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MedWorm: Alport Syndrome



MedWorm.com provides a medical RSS filtering service. Over 7000 RSS medical sources are combined and output via different filters. This feed contains the latest news and research in the Alport Syndrome category.



Last Build Date: Tue, 22 Mar 2016 08:29:46 +0100

 



RAAS inhibition and the course of Alport Syndrome

Fri, 18 Mar 2016 00:00:00 +0100

Publication date: Available online 16 March 2016 Source:Pharmacological Research Author(s): Isavella Savva, Alkis Pierides, Constantinos Deltas Alport syndrome (AS) is a hereditary progressive glomerulonephritis with a high life-time risk for end-stage renal disease (ESRD). Most patients will reach ESRD before the age of 30 years, while a subset of them with milder mutations will do so at older ages, even after 50 years. Frequent extrarenal manifestations are hearing loss and ocular abnormalities. AS is a genetically heterogeneous collagen IV nephropathy, with 85% of the cases caused by mutations in the X-linked COL4A5 gene and the rest by homozygous or compound heterozygous mutations in either the COL4A3 or the COL4A4 gene on chromosome 2q36-37. There is no radical cure for the disea...

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Reply to: Cataract surgery in patients with Alport syndrome.

Fri, 26 Feb 2016 00:00:00 +0100

Authors: Ecsedy M, Nagy ZZ PMID: 26951527 [PubMed - as supplied by publisher] (Source: European Journal of Ophthalmology)



Cataract surgery in patients with Alport syndrome.

Fri, 26 Feb 2016 00:00:00 +0100

Authors: Bellini LP, Brum GS PMID: 26951528 [PubMed - as supplied by publisher] (Source: European Journal of Ophthalmology)






[Anteroposterior lenticonus in a patient with Alport syndrome].

Mon, 08 Feb 2016 20:33:02 +0100

Authors: Jait A, Lezrek M, Lezrek O, ELatiqi MA, Boutimzine N, Daoudi R PMID: 26852385 [PubMed - as supplied by publisher] (Source: Journal Francais d Ophtalmologie)



Contact lens fitting in a patient with Alport syndrome and posterior polymorphous corneal dystrophy: a case report

Tue, 02 Feb 2016 13:36:02 +0100

ABSTRACT Alport Syndrome is a hereditary disease that is caused by a gene mutation and affects the production of collagen in basement membranes; this condition causes hemorrhagic nephritis associated with deafness and ocular changes. The X-linked form of this disease is the most common and mainly affects males. Typical ocular findings are dot-and-fleck retinopathy, anterior lenticonus, and posterior polymorphous corneal dystrophy. Some cases involving polymorphous corneal dystrophy and corneal ectasia have been previously described. Here we present a case report of a 33-year-old female with Alport syndrome, posterior polymorphous corneal dystrophy, and irregular astigmatism, whose visual acuity improved with a rigid gas permeable contact lens.RESUMO A síndrome de Alport é descrita como u...

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Familial focal segmental glomerulosclerosis: mutation in inverted formin 2 mimicking Alport syndrome.

Mon, 01 Feb 2016 00:00:00 +0100

Authors: Rood IM, Bongers EM, Lugtenberg D, Klein IH, Steenbergen EJ, Wetzels JF, Deegens JK Abstract Focal segmental glomerulosclerosis (FSGS) is one of the most common patterns of glomerular injury. FSGS can be caused by mutations in genes encoding proteins that play key roles in the function of the podocyte and glomerular basement membrane. In this case report we present a family with FSGS initially suspected to be Alport syndrome. Genetic analysis according to the Dutch guidelines of FSGS revealed a mutation in INF2. PMID: 26951353 [PubMed - in process] (Source: The Netherlands Journal of Medicine)



Quantitative Micro-Computed Tomography Imaging of Vascular Dysfunction in Progressive Kidney Diseases

Fri, 29 Jan 2016 00:00:00 +0100

Progressive kidney diseases and renal fibrosis are associated with endothelial injury and capillary rarefaction. However, our understanding of these processes has been hampered by the lack of tools enabling the quantitative and noninvasive monitoring of vessel functionality. Here, we used micro-computed tomography (µCT) for anatomical and functional imaging of vascular alterations in three murine models with distinct mechanisms of progressive kidney injury: ischemia-reperfusion (I/R, days 1–56), unilateral ureteral obstruction (UUO, days 1–10), and Alport mice (6–8 weeks old). Contrast-enhanced in vivo µCT enabled robust, noninvasive, and longitudinal monitoring of vessel functionality and revealed a progressive decline of the renal relative blood volume in al...



Podocyte p53 Limits the Severity of Experimental Alport Syndrome

Thu, 31 Dec 2015 00:00:00 +0100

Alport syndrome (AS) is one of the most common types of inherited nephritis caused by mutation in one of the glomerular basement membrane components. AS is characterized by proteinuria at early stage of the disease and glomerular hyperplastic phenotype and renal fibrosis at late stage. Here, we show that global deficiency of tumor suppressor p53 significantly accelerated AS progression in X-linked AS mice and decreased the lifespan of these mice. p53 protein expression was detected in 21-week-old wild-type mice but not in age-matched AS mice. Expression of proinflammatory cytokines and profibrotic genes was higher in p53+/– AS mice than in p53+/+ AS mice. In vitro experiments revealed that p53 modulates podocyte migration and positively regulates the expression of podocyte-specific g...



Renal denervation in a patient with Alport syndrome and rejected renal allograft

Sun, 20 Dec 2015 00:00:00 +0100

Publication date: Available online 20 December 2015 Source:Indian Heart Journal Author(s): Narayana Raju, Vincent Lloyd, Sachin Yalagudri, Bharati Das, A.G. Ravikishore Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome...



Laminations and microgranule formation in pediatric glomerular basement membranes.

Tue, 15 Dec 2015 18:12:02 +0100

Authors: Craver R, Crespo-Salgado J, Aviles D Abstract Glomerular basement membrane (GBM) splitting, laminations, and microgranular formation are classically encountered with Alport disease, but can be found in other glomerular diseases. We found moderate to marked GBM laminations/microgranular formations in 51 of 724 (7%) pediatric diagnostic renal biopsies. These included 12 Alport disease, 12 thin basement membrane disease (TBM), 13 mesangial hypercellularity (MH), 6 focal segmental glomerulosclerosis (FSGS), and 8 other diseases. Follow-up demonstrated progression in most of the Alport disease and FSGS, as expected, but also in 40% of TBM and 30% of MH. Basement membrane laminations/microgranular formations are not specific for Alport disease, may represent a non-specific injur...

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Capsulorhexis tearing pattern during phacoemulsification in anterior lenticonus due to Alport syndrome.

Mon, 14 Dec 2015 00:00:00 +0100

CONCLUSIONS: Knowing this tearing pattern preoperatively can help to prevent capsule runoff and capsule rupture. PMID: 26692055 [PubMed - as supplied by publisher] (Source: European Journal of Ophthalmology)



Comprehensive management of diffuse leiomyomatosis in a patient with Alport syndrome.

Wed, 02 Dec 2015 13:25:29 +0100

Authors: Burgos R, Muñiz E, Rosa ER, Olivares CJ, Romaguera J Abstract Alport syndrome with diffuse leiomyomatosis (ASDL) is a complex combination that doesn't have a specific course of treatment. In this case report, we present a 44-year-old woman with ASDL and detail her treatment. The patient presented at the emergency room (ER) with symptoms of anemia, bronchial asthma, and abnormal uterine bleeding (AUB). The patient had diffuse myomas in different areas of her body, including the esophagus and genital tract. She was treated by a multidisciplinary team that included members from the hematology/oncology, pulmonary, interventional radiology, anesthesia, surgery, and gynecology services. A physician from interventional radiology performed an embolization of the uterine arteries ...



Alport syndrome and pregnancy: Good obstetric and nephrological outcomes in a pregnant woman with homozygous autosomal recessive Alport syndrome

Wed, 02 Dec 2015 00:00:00 +0100

We describe the course of pregnancy in a 27‐year‐old woman with homozygous autosomal recessive Alport syndrome. Genetic analysis revealed a homozygous COL4A4 mutation in exon 36 (c.3307G > A) with p.G1102R inherited from her parents (who were parallel cousins) 1 year before conception. Before pregnancy, the patient’s renal function and blood pressure were normal, and her urinary protein excretion was below 2 g/day. The pregnancy course was uneventful in the first and second trimesters. She was detected to have nephrotic‐range proteinuria during the third trimester, but was observed closely on an outpatient basis without any medications, as her general condition was good, her renal function and blood pressure remained stable, and the fetal well‐being was maintained. At 39+0 wee...



Isolated microscopic haematuria of glomerular origin: clinical significance and diagnosis in the 21st century.

Tue, 01 Dec 2015 00:00:00 +0100

Authors: Chan MM, Gale DP Abstract Isolated microscopic, or non-visible, haematuria of glomerular origin was previously regarded a benign finding, but it is now known that, even in the absence of proteinuria, hypertension or renal impairment at presentation, haematuria is associated with increased risk of kidney failure in the long term. The most common causes of isolated microscopic haematuria among children and young adults are IgA nephropathy, Alport syndrome (AS), and thin basement membrane nephropathy (TBMN). AS, which is usually inherited as an X-linked or autosomal recessive trait, and TBMN, which is usually autosomal dominant, are caused by mutations in the genes encoding type-IV collagen, an abundant component of the glomerular basement membrane. A detailed family history ...



Generation of induced pluripotent stem cells from renal tubular cells of a patient with Alport syndrome.

Sat, 28 Nov 2015 22:13:28 +0100

In this study, we generated iPSCs from renal tubular cells via ectopic expression of four transcription factors (Oct4, Sox2, c-myc, and Klf4). According to the human embryonic stem cell (hESC) charter, iPSC formation was confirmed by comparatively analyzing hESC markers via colony morphology, immunohistochemistry, qRT-PCR, flow cytometry, gene expression profiling of the three germ layers, and karyotyping. Our results demonstrated that iPSCs were similar to hESCs with regard to morphology, proliferation, hESC-specific surface marker expression, and differentiation into the cell types of the three germ layers. The efficient generation of iPSCs from the renal tubular cells of an AS patient would provide a novel model to investigate the mechanisms underlying AS and to develop new treatments f...

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A COL4A5 mutation with glomerular disease and signs of chronic thrombotic microangiopathy

Fri, 20 Nov 2015 00:00:00 +0100

COL4A5 mutations are a known cause of Alport syndrome, which typically manifests with haematuria, hearing loss and ocular symptoms. Here we report on a 16-year-old male patient with a negative family history who presented with proteinuria, progressive renal failure and haemolysis, but without overt haematuria or hearing loss. A renal biopsy revealed features of atypical IgA nephropathy, while a second biopsy a year later showed features of focal segmental glomerulosclerosis, but was finally diagnosed as chronic thrombotic microangiopathy. Targeted sequencing of candidate genes for steroid-resistant nephrotic syndrome and congenital thrombotic microangiopathy was negative. Despite all therapeutic efforts, including angiotensin-converting enzyme inhibition, immunosuppressive therapy, plasma ...



X-linked Alport syndrome associated with a synonymous p.Gly292Gly mutation alters the splicing donor site of the type IV collagen alpha chain 5 gene

Wed, 18 Nov 2015 00:00:00 +0100

Conclusions This is the first report of a synonymous COL4A5 substitution being responsible for XLAS. Our findings suggest that transcript analysis should be conducted for the future correct assessment of silent mutations. (Source: Clinical and Experimental Nephrology)



Combined Alport syndrome and Klinefelter syndrome

Tue, 10 Nov 2015 00:00:00 +0100

Abstract To date, there have been a very limited number of case reports on combined Alport syndrome (AS) and Klinefelter syndrome (KS). We herein describe the case of a 9‐month‐old boy diagnosed with concomitant AS and KS. KS was detected on chromosomal analysis of the amniotic fluid, and hematuria/proteinuria was identified in urinary screening at 6 months of age. Renal biopsy indicated AS, with complete deficit of the α5 chain of type IV collagen in the glomerular basement membranes. On genetic analysis for AS, de novo homozygote mutation (c.3605‐2a > c) was seen in the gene encoding α5 chain of type IV collagen (COL4A5) on the X chromosomes of maternal origin. This is the first case report of combined AS and KS diagnosed during infancy, and it indicates the need to consider...



Analysis of histopathological pattern of kidney biopsy specimens in Kuwait: A single-center, five-year prospective study.

Sun, 01 Nov 2015 00:00:00 +0100

Authors: Abdallah E, Al-Helal B, Asad R, Kannan S, Draz W, Abdelgawad Z Abstract Glomerulonephritis (GN) varies in incidence in different geographical areas due to different socioeconomic conditions and ethnicity, genetic variability and environmental factors. Our study is aimed to determine the histopathological pattern of kidney biopsies in Kuwait over the preceding five years. In a prospective study, we analyzed the clinical and pathological data of 214 kidney biopsies that were performed during the period from November 2009 to November 2014 at the Al-Khezam Dialysis Center, Al-Adan Hospital, Kuwait. Kidney biopsies were performed percutaneously using an automated gun guided by ultrasound. The biopsy samples were processed for light microscopy and immunofluorescence. Electron mi...



Robotic-assisted kidney transplantation: our first case

Fri, 28 Aug 2015 00:00:00 +0100

Conclusion We present the first Spanish transperitoneal pure RAKT from a living-related donor. We believe this is the second pure robotic-assisted kidney transplantation case performed in Europe. We believe that the potential advantages of RAKT are related to the quality of the vascular anastomosis, the possible lower complication rate and the shorter recovery of the recipients. (Source: World Journal of Urology)

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Phenotypic heterogeneity in females with X-linked Alport syndrome.

Fri, 07 Aug 2015 00:00:00 +0100

CONCLUSIONS: The current case report demonstrates the importance of considering skewed X-inactivation in females who exhibit signs or symptoms of Xlinked disorders. PMID: 26249550 [PubMed - as supplied by publisher] (Source: Clinical Nephrology)



Long-term treatment by ACE inhibitors and angiotensin receptor blockers in children with Alport syndrome

Fri, 07 Aug 2015 00:00:00 +0100

Conclusion Our findings demonstrate that early and long-term ACEi and ARB treatments in children with AS is efficient and well tolerated. The antiproteinuric effect of ACEi and ARB is of equal value in children with severe and less severe mutations in the COL4An gene. (Source: Pediatric Nephrology)



Role of Platelet-Derived Growth Factor-CC in Capillary Rarefaction in Renal Fibrosis.

Sat, 01 Aug 2015 00:00:00 +0100

Authors: Boor P, Bábíčková J, Steegh F, Hautvast P, Martin IV, Djudjaj S, Nakagawa T, Ehling J, Gremse F, Bücher E, Eriksson U, van Roeyen CR, Eitner F, Lammers T, Floege J, Peutz-Kootstra CJ, Ostendorf T Abstract We have identified platelet-derived growth factor (PDGF)-CC as a potent profibrotic mediator in kidney fibrosis and pro-angiogenic mediator in glomeruli. Because renal fibrosis is associated with progressive capillary rarefaction, we asked whether PDGF-CC neutralization in fibrosis might have detrimental anti-angiogenic effects leading to aggravated peritubular capillary loss. We analyzed capillary rarefaction in mice with and without PDGF-CC neutralization (using genetically deficient mice and neutralizing antibodies), in three different models of renal interstitial...



Study of the True Clinical Progression of Autosomal Dominant Alport Syndrome in a European Population

Fri, 31 Jul 2015 19:49:17 +0100

Conclusions: Our results suggest that dominant patterns are accompanied by a severe clinical expression that can be superimposed to the recessive and X chromosome-linked patterns, contrary to what has been classically stated. The high phenotypic variability observed in the families lead to the fact that many cases go unnoticed and the severest cases are erroneously diagnosed as recessive, which means that the real prevalence of dominant forms is probably higher than the current 5%.Kidney Blood Press Res 2015;40:435-442 (Source: Kidney and Blood Pressure Research)



Role of Platelet-Derived Growth Factor-CC in Capillary Rarefaction in Renal Fibrosis

Sat, 25 Jul 2015 17:09:15 +0100

We have identified platelet-derived growth factor (PDGF)-CC as a potent profibrotic mediator in kidney fibrosis and pro-angiogenic mediator in glomeruli. Because renal fibrosis is associated with progressive capillary rarefaction, we asked whether PDGF-CC neutralization in fibrosis might have detrimental anti-angiogenic effects leading to aggravated peritubular capillary loss. We analyzed capillary rarefaction in mice with and without PDGF-CC neutralization (using genetically deficient mice and neutralizing antibodies), in three different models of renal interstitial fibrosis, unilateral ureteral obstruction, unilateral ischemia-reperfusion, Col4a3-deficient (Alport) mice, and healthy animals. (Source: American Journal of Pathology)

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Glomerular basement membrane disorders and the kidney

Wed, 22 Jul 2015 00:00:00 +0100

The glomerular basement membrane (GBM) is the vital barrier between blood and glomerular filtrate. Diseases that damage it generally cause haematuria initially, but as architecture becomes disordered proteinuria becomes an increasing feature. Inflammatory glomerulonephritis most commonly does this, but genetic abnormalities of GBM components are another important mechanism. Alport's syndrome, a hereditary nephritis associated with deafness, is the second commonest genetic cause of renal failure. (Source: Medicine)






Genotype-phenotype Correlation of the p.R1165C Mutation in the MYH9 Disorder: Report of a Japanese Pedigree

Sat, 18 Jul 2015 12:49:59 +0100

We report a Japanese pedigree wherein the MYH9 p.R1165C mutation was present in over 4 generations. Three individuals were misdiagnosed as Bernard-Soulier syndrome carriers. Among the 12 patients with abnormal hematological features, the proband’s mother, aunt, and grandaunt presented with sensorineural hearing impairment, and the mother presented with presenile cataract, and nephritis. This case report confirms the previously established genotype-phenotype correlations of the MYH9 disorder that p.R1165C is associated with variable expression of nonhematological manifestations. Careful detection of leukocyte inclusion bodies in peripheral blood smears is necessary to prevent misdiagnosis. (Source: Journal of Pediatric Hematology Oncology)



Carriers of Autosomal Recessive Alport Syndrome with Thin Basement Membrane Nephropathy Presenting as Focal Segmental Glomerulosclerosis in Later Life

Fri, 17 Jul 2015 18:27:52 +0100

Collagen IV nephropathies (COL4Ns) comprise benign familial microscopic hematuria, thin basement membrane nephropathy (TBMN), X-linked Alport syndrome (AS) and also autosomal recessive and dominant AS. Apart from the X-linked form of AS, which is caused by hemizygous mutations in the COL4A5 gene, the other entities are caused by mutations in the COL4A3 or COL4A4 genes. The diagnosis of these conditions used to be based on clinical and/or histological findings of renal biopsies, but it is the new molecular genetics approach that revolutionised their investigation and proved particularly instrumental, especially, in many not so clear-cut cases. More recently, the spectrum of COL4N has expanded to include late onset focal segmental glomerulosclerosis (FSGS) that develops on top of TBMN in lat...



Chinese family with diffuse oesophageal leiomyomatosis: a new COL4A5/COL4A6 deletion and a case of gonosomal mosaicism

Thu, 16 Jul 2015 00:00:00 +0100

Conclusions: This is the first report of gonadosomal mosaicism associated to DOL-AS (Source: BMC Medical Genetics)

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Intermittent bacteremia detected in an asymptomatic apheresis platelet donor with repeat positive culture for Escherichia coli: a case report.

Tue, 14 Jul 2015 00:00:00 +0100

CONCLUSION: This asymptomatic donor has intermittent bacteremia likely related to diverticular disease. Isolation of E. coli twice prompted further investigation and donor deferral. PMID: 26172444 [PubMed - as supplied by publisher] (Source: Transfusion)



Crescentic and necrotising glomerulonephritis: a rare histological manifestation of Alport syndrome

Fri, 19 Jun 2015 00:00:00 +0100

Alport syndrome (AS) is a generalised inherited disease characterised by haematuria, progressive renal failure, sensorineural deafness and ocular abnormalities.1 X-linked AS, resulting from mutations of the type IV collagen α5 (COL4A5) gene encoding the type IV collagen α5 chain, accounts for 85% of AS. To date, nearly 700 COL4A5 mutations have been reported, with about 45% of them being missense mutations. The remainder of the patients with AS have autosomal recessive, or rarely, an autosomal dominant inheritance, both of which result from mutations in the COL4A3 or COL4A4 gene.2 Diagnosis of AS relies on clinical presentation, immunohistochemical analysis of the collagen α (IV) chains in the skin and/or renal biopsy specimen, ultrastructural changes of the glomerular ba...



Improved genetic counseling in Alport syndrome by new variants of COL4A5 gene

Tue, 09 Jun 2015 00:00:00 +0100

We describe the first reported case of COL4A5 gene missense c.1499 G > T mutation in a 16‐year‐old girl confirmed to be affected by Alport Syndrome after genetic counseling. Next Generation Sequencing procedures let discover this mutation and offer an accurate clinical treatment to this patient. Current scientific understanding of genetic syndromes suggests the high importance of updated databases and the inclusion of Variant of Unknown Significance related to clinical cases. All of this updating could enable patients to have a better opportunity of diagnosis and having genetic and clinical counseling. This event is even more important in women planning to start a family to have correct genetic counseling regarding the risk posed to offspring, and allowing the decision to underg...



Outcomes of Renal Transplantation in Patients With Alport Syndrome

Mon, 01 Jun 2015 00:00:00 +0100

We evaluated the outcomes of patients who underwent renal transplantation (Rtx) due to end-stage renal disease (ESRD) related to Alport syndrome in our study. (Source: Transplantation Proceedings)



Somatic mosaicism and variant frequency detected by next-generation sequencing in X-linked Alport syndrome

Wed, 27 May 2015 00:00:00 +0100

Authors: Xue Jun Fu, Kandai Nozu, Hiroshi Kaito, Takeshi Ninchoji, Naoya Morisada, Koichi Nakanishi, Norishige Yoshikawa, Hiromi Ohtsubo, Natsuki Matsunoshita, Naohiro Kamiyoshi, Chieko Matsumura, Nobuaki Takagi, Kohei Maekawa, Mariko Taniguchi-Ikeda & Kazumoto Iijima (Source: European Journal of Human Genetics)

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Sp893 * morphological alterations of podocytes in alport syndrome by low vacuum scanning electron microscopy

Thu, 21 May 2015 00:00:00 +0100

(Source: Nephrology Dialysis Transplantation)



A Multidrug, Antiproteinuric Approach to Alport Syndrome: A Ten-Year Cohort Study

Mon, 20 Apr 2015 13:28:25 +0100

Conclusion: The Remission Clinic approach safely ameliorated albuminuria, blood pressure, lipids, and glomerular selectivity in AS patients and halted long-term progression in those without renal insufficiency to start with.Nephron (Source: Nephron)



Transplanting Sibling Love

Tue, 14 Apr 2015 00:00:00 +0100

https://www.youtube.com/watch?v=hFO6COuAhWg For his entire life, radio host James Rabe has known that one day he’d need a new kidney. A disease called Alport Syndrome slowly caused his kidneys to fail. As his condition advanced, the search for a new organ began. His big sister stepped up and gave part of herself so her little brother [...] (Source: News from Mayo Clinic)

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Femtosecond laser-assisted cataract surgery in Alport syndrome with anterior lenticonus.

Thu, 09 Apr 2015 00:00:00 +0100

CONCLUSIONS: Femtosecond laser cataract surgery can be a safe and successful method for optical rehabilitation of anterior lenticonus in patients with Alport syndrome. PMID: 25907292 [PubMed - as supplied by publisher] (Source: European Journal of Ophthalmology)



Extensive preoperative workup in diffuse esophageal leiomyomatosis associated with Alport syndrome influences surgical treatment: A case report

Wed, 01 Apr 2015 00:00:00 +0100

Conclusion EUS and 3D-GCT should strongly be considered as part of routine preoperative workup in these patients. (Source: International Journal of Surgery Case Reports)



Translational value of animal models of kidney failure.

Tue, 24 Mar 2015 00:00:00 +0100

Authors: Ortiz A, Sanchez-Niño MD, Izquierdo MC, Martin-Cleary C, Garcia-Bermejo L, Moreno JA, Ruiz-Ortega M, Draibe J, Cruzado JM, Garcia-Gonzalez MA, Lopez-Novoa JM, Soler MJ, Sanz AB, Red de Investigacion Renal (REDINREN) and Consorcio Madrileño para investigación del fracaso renal agudo (CIFRA) Abstract Acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with decreased renal function and increased mortality risk, while the therapeutic armamentarium is unsatisfactory. The availability of adequate animal models may speed up the discovery of biomarkers for disease staging and therapy individualization as well as design and testing of novel therapeutic strategies. Some longstanding animal models have failed to result in therapeutic advances in the clinical ...



Characterization of the Intrarenal Renin-Angiotensin System in Experimental Alport Syndrome.

Sat, 14 Mar 2015 00:00:00 +0100

In conclusion, progressive kidney injury in AS is associated with changes in expression of intrarenal renin Ang system components and Ang peptides. HO-1 and ACE2 may represent novel markers of AS-associated kidney injury, whereas administration of recombinant ACE2 and/or Ang-(1-7) may represent novel therapeutic approaches in AS. PMID: 25777062 [PubMed - as supplied by publisher] (Source: Am J Pathol)



Characterization of the Intrarenal Renin-Angiotensin System in Experimental Alport Syndrome

Sat, 14 Mar 2015 00:00:00 +0100

Blockade of the renin-angiotensin system attenuates the progression of experimental and clinical Alport syndrome (AS); however, the underlying mechanism(s) remains largely unknown. We evaluated the renin-angiotensin system in 4- and 7-week-old homozygous for collagen, type IV, α3 gene (Col4A3−/−) and wild-type mice, a model of AS characterized by proteinuria and progressive renal injury. Renal angiotensin (Ang) II levels increased, whereas renal Ang-(1–7) levels decreased in 7-week-old Col4a3−/− mice compared with age-matched controls; these changes were partially reversed by recombinant angiotensin-converting enzyme 2 (ACE2) treatment. (Source: American Journal of Pathology)

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Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

Wed, 11 Mar 2015 00:00:00 +0100

Publication date: Available online 27 February 2015 Source:Molecular Genetics and Metabolism Author(s): Shan Chen , Monica Grover , Tarek Sibai , Jennifer Black , Nahid Rianon , Abbhirami Rajagopal , Elda Munivez , Terry Bertin , Brian Dawson , Yuqing Chen , Ming-Ming Jiang , Brendan Lee , Tao Yang , Yangjin Bae Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknow...



Phacoemulsification with toric IOL implantation in Alport syndrome with anterior lenticonus having spontaneously ruptured anterior capsule.

Mon, 02 Mar 2015 00:00:00 +0100

CONCLUSIONS: Safe phacoemulsification with toric IOL implantation is possible in cases with spontaneous rupture of anterior lens capsule. Ability to achieve compact and complete capsulorhexis is one of the key steps to achieve favorable results. PMID: 25743777 [PubMed - as supplied by publisher] (Source: European Journal of Ophthalmology)



Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples.

Sun, 01 Mar 2015 00:00:00 +0100

In this study, Solexa sequencing was used to identify and quantitatively profile small RNAs from an AS family. We identified 30 known miRNAs that showed a significant change in expression between two individuals. Nineteen miRNAs were up-regulated and eleven were down-regulated. Forty-nine novel miRNAs showed significantly different levels of expression between two individuals. Gene target predictions for the miRNAs revealed that high ranking target genes were implicated in cell, cell part and cellular process categories. The purine metabolism pathway and mitogen-activated protein kinase (MAPK) signaling pathway were enriched by the largest number of target genes. These results strengthen the notion that miRNAs and their target genes are involved in AS and the data advance our understanding...



Evidence of digenic inheritance in Alport syndrome

Wed, 18 Feb 2015 00:00:00 +0100

Conclusions Segregation analysis indicated three possible digenic segregation models: (i) autosomal inheritance with mutations on different chromosomes, resembling recessive inheritance (five families); (ii) autosomal inheritance with mutations on the same chromosome resembling dominant inheritance (two families) and (iii) unlinked autosomal and X-linked inheritance having a peculiar segregation (four families). This pedigree analysis provides evidence for digenic inheritance of Alport syndrome. Clinical geneticists and nephrologists should be aware of this possibility in order to more accurately assess inheritance probabilities, predict prognosis and identify other family members at risk. (Source: Journal of Medical Genetics)



Ocular Features in Alport Syndrome: Pathogenesis and Clinical Significance.

Tue, 03 Feb 2015 00:00:00 +0100

Authors: Savige J, Sheth S, Leys A, Nicholson A, Mack HG, Colville D Abstract Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular ...

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Evaluation of Genetic Renal Diseases in Potential Living Kidney Donors

Thu, 15 Jan 2015 00:00:00 +0100

Abstract Better outcomes for living donor transplantation, together with the shortened waiting time and the increasing gap between supply and demand for kidneys for transplantation, has led to greater pressure on transplant candidates and transplant centers alike to encourage and advocate for living kidney donation as the more timely form of renal replacement therapy. Recent studies report that living kidney donors biologically related to their transplant candidate may be at increased risk of end-stage renal disease (ESRD) and this may reflect the shared inheritance of a disease or risk allele. The possibility of carrying a genetic predisposition or the renal disease itself should be entertained in every kidney donor with a positive family history of kidney disease. Screening labo...



Diffuse Alveolar Haemorrhage: A Fatal Complication After Alemtuzumab Induction Therapy in Renal Transplantation

Thu, 01 Jan 2015 00:00:00 +0100

We report a fatal case of alemtuzumab-induced diffuse alveolar hemorrhage in an 18-year-old male with Alport syndrome. The patient developed acute onset shortness of breath, hemoptysis and fever after renal transplantation. Computed tomography findings were consistent with adult respiratory distress syndrome. Bronchoscopy and broncho-alveolar lavage was performed that showed no evidence of pathogenic bacteria or opportunistic infection. The patient was intubated and ventilated because of worsening respiratory function. (Source: Transplantation Proceedings)



The challenges and outcomes of living donor kidney transplantation in pediatric and adolescent age group in a developing country: A critical analysis from a single center of north India

Thu, 01 Jan 2015 00:00:00 +0100

Conclusions: The spectrum of etiology of ESRD differs in our patients from the west, with chronic glomerulonephritis being the most common etiology. Early graft survival is comparable, but the 5-year graft survival is clearly inferior as compared with developed countries. (Source: Indian Journal of Urology)



An unusual case of extensive peritoneal calcification: A case report

Thu, 18 Dec 2014 00:00:00 +0100

We report an uncommon case of extensive peritoneal calcification in a 39-year-old female without long exposure to peritoneal dialysis solutions, in which peritoneal calcification could be linked to Alport syndrome and previous adverse reaction to intraperitoneal iodinated contrast. Radiologist should be aware of this and related imaging findings, know when to search for them as well as understand their clinical value. (Source: European Journal of Radiology Open)



Utility of renal biopsy in the clinical management of renal disease

Wed, 17 Dec 2014 15:40:08 +0100

This provocative article describes underutilization of kidney biopsies in the diagnosis and prognosis of renal disease.  The authors state that kidney biopsies can aid in the better management of patients with renal disease at all stages. : Atypical Hemolytic–Uremic Syndrome Expert guidelines for the management of alport syndrome and thin basement membrane nephropathy. Indications for renal revascularization—the landscape after the ASTRAL study (Source: Nephrology Now)

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Effects of mycophenolate mofetil on kidney function and phosphorylation status of renal proteins in Alport COL4A3-deficient mice

Wed, 10 Dec 2014 00:00:00 +0100

Conclusions: These data suggest that the MMF treatment in this murine model moderately improved kidney function and reversed the phosphorylation status of six renal phosphoprotein spots to that seen in WT mice. (Source: Proteome Science)



Chronic kidney disease: MicroRNA inhibition in Alport syndrome

Tue, 09 Dec 2014 00:00:00 +0100

Nature Reviews Nephrology 11, 64 (2015). doi:10.1038/nrneph.2014.234 Inhibition of microRNA (miRNA)-21 could represent a therapeutic strategy for the treatment of chronic kidney diseases, including Alport nephropathy, say the researchers of a new study. Gomez et al. assessed the therapeutic potential of highly specific oligonucleotides that distribute to the kidney and (Source: Nature Reviews Nephrology)



Alport syndrome with phenotypic marfanoid habitus: atypical case series

Fri, 05 Dec 2014 08:00:00 +0100

Authors: N Agrawal, D P Nayak, P Gupta, A Haripriya & P Bhuwania (Source: Eye)



Alport syndrome in a Kazakh family: a case study.

Mon, 01 Dec 2014 00:00:00 +0100

Authors: Zholdybayeva EV, Rakhimova SE, Baikara BT, Nigmatullina NB, Mustapayeva NM, Momynaliev KT PMID: 25572247 [PubMed - in process] (Source: Journal of Genetics)



Improving Mutation Screening in Familial Hematuric Nephropathies through Next Generation Sequencing

Fri, 28 Nov 2014 00:00:00 +0100

Alport syndrome is an inherited nephropathy associated with mutations in genes encoding type IV collagen chains present in the glomerular basement membrane. COL4A5 mutations are associated with the major X-linked form of the disease, and COL4A3 and COL4A4 mutations are associated with autosomal recessive and dominant forms (thought to be involved in 15% and 1%–5% of the families, respectively) and benign familial hematuria. Mutation screening of these three large genes is time-consuming and expensive. Here, we carried out a combination of multiplex PCR, amplicon quantification, and next generation sequencing (NGS) analysis of three genes in 101 unrelated patients. We identified 88 mutations and 6 variations of unknown significance on 116 alleles in 83 patients. Two additional indel m...

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Pathology vs. molecular genetics: (re)defining the spectrum of Alport syndrome

Wed, 26 Nov 2014 00:00:00 +0100

Kidney International 86, 1081 (December 2014). doi:10.1038/ki.2014.326 Author: Jeffrey H Miner (Source: Kidney International)



Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis

Wed, 26 Nov 2014 00:00:00 +0100

Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis Kidney International 86, 1253 (December 2014). doi:10.1038/ki.2014.305 Authors: Andrew F Malone, Paul J Phelan, Gentzon Hall, Umran Cetincelik, Alison Homstad, Andrea S Alonso, Ruiji Jiang, Thomas B Lindsey, Guanghong Wu, Matthew A Sparks, Stephen R Smith, Nicholas J A Webb, Philip A Kalra, Adebowale A Adeyemo, Andrey S Shaw, Peter J Conlon, J Charles Jennette, David N Howell, Michelle P Winn & Rasheed A Gbadegesin (Source: Kidney International)



Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

Sat, 22 Nov 2014 19:15:03 +0100

MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously and evaluated the therapeutic potential of these anti–miR-21 oligonucleotides in chronic kidney disease. In a murine model of Alport nephropathy, miR-21 silencing did not produce any adverse effects and resulted in substantially milder kidney disease, with minimal albuminuria and dysfunction, compared with vehicle-treated mice. miR-21 silencing dramatically improved survival of Alport mice and redu...



End-stage kidney disease due to Alport syndrome: outcomes in 296 consecutive Australia and New Zealand Dialysis and Transplant Registry cases

Fri, 21 Nov 2014 00:00:00 +0100

Conclusion Alport syndrome patients experienced comparable dialysis and renal transplant outcomes to matched non-Alport ESKD controls in the contemporary cohort due to relatively greater improvements in outcomes for non-Alport ESKD patients over time. Post-transplant anti-GBM disease was rare. (Source: Nephrology Dialysis Transplantation)



Successful peritoneal dialysis in 2 siblings with Alport's disease and gastric pull-up.

Fri, 14 Nov 2014 23:12:51 +0100

Authors: Vellanki VS, Bargman JM PMID: 25075002 [PubMed - in process] (Source: Peritoneal Dialysis International)

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Clinical utility gene card for: Alport syndrome – update 2014

Wed, 12 Nov 2014 00:00:00 +0100

Clinical utility gene card for: Alport syndrome – update 2014 European Journal of Human Genetics advance online publication, November 12 2014. doi:10.1038/ejhg.2014.254 Authors: Jens Michael Hertz, Mads Thomassen, Helen Storey & Frances Flinter (Source: European Journal of Human Genetics)



Whole exome sequencing reveals novel COL4A3 and COL4A4 mutations and resolves diagnosis in Chinese families with kidney disease

Fri, 07 Nov 2014 00:00:00 +0100

Conclusion: WES identified 2 novel and 2 known pathogenic COL4A3/COL4A4/COL4A5 mutations in 3 families with previously unexplained inherited kidney disease. These findings highlight the clinical range of collagen IV-related nephropathies and resolved diagnostic confusion arising from atypical or incomplete clinical/histological findings, allowing appropriate counselling and treatment advice to be given. (Source: BMC Nephrology)



Morphological diagnosis of Alport syndrome and thin basement membrane nephropathy by low vacuum scanning electron microscopy.

Sat, 01 Nov 2014 13:15:04 +0100

Authors: Okada S, Inaga S, Kitamoto K, Kawaba Y, Nakane H, Naguro T, Kaidoh T, Kanzaki S Abstract Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are genetic disorders caused by mutations of the type IV collagen genes COL4A3, COL4A4, and/or COL4A5. We here aimed to investigate the three-dimensional ultrastructure of the glomerular basement membrane (GBM) in order to introduce a novel method of diagnosing AS and TBMN. The subjects were 4 patients with AS and 6 patients with TBMN. Conventional renal biopsy paraffin sections from AS and TBMN patients were stained with periodic acid methenamine silver (PAM) and observed directly under low vacuum scanning electron microscopy (LVSEM). The PAM-positive GBMs were clearly visible under LVSEM through the overlying cellular...



Clinicopathological Analysis of 155 Patients with Persistent Isolated Hematuria

Sat, 01 Nov 2014 00:00:00 +0100

Conclusions Close follow-up should be required as the primary management for PIH. Equally important is careful monitoring for early identification of undesirable predictors; while renal biopsy and other timely intervention are warranted if there is hypertension, significant proteinuria or renal impairment. (Source: Chinese Medical Sciences Journal)



A new mutation in the COL4A3 gene responsible for autosomal dominant Alport syndrome, which only generates hearing loss in some carriers.

Tue, 28 Oct 2014 00:00:00 +0100

We report a family that suffers an autosomal dominant Alport syndrome caused by a previously undescribed mutation in the COL4A3 gene, in which several members have hearing impairment as the only clinical manifestation, suggesting that in this family deafness can occur independent of renal disease. This mutation is also present in a patient with anterior lenticonus, an observation only found in families with recessive and sex-linked Alport disease. PMID: 25450602 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics)

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Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families.

Mon, 13 Oct 2014 00:00:00 +0100

Authors: Sá MJ, Storey H, Flinter F, Nagel M, Sampaio S, Castro R, Araújo JA, Gaspar MA, Soares C, Oliveira A, Henriques AC, Costa AG, Abreu CP, Ponce P, Alves R, Pinho L, Silva SE, Moura CP, Mendonça L, Carvalho F, Pestana M, Alves S, Carvalho F, Oliveira JP Abstract Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathoge...



Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Mon, 13 Oct 2014 00:00:00 +0100

In this study, 22 out of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in...



Kidney diseases in Roma and non-Roma children from eastern Slovakia: are Roma children more at risk?

Tue, 30 Sep 2014 20:46:47 +0100

Conclusions The overall proportion of Roma children in outpatients with kidney problems is smaller than the estimated proportion of Roma in all children in Slovakia, in particular for early signs, but not for major renal diseases. (Source: International Journal of Public Health)



A novel cardiovascular presentation of Alport Syndrome: Spontaneous coronary artery dissection

Thu, 25 Sep 2014 00:00:00 +0100

A 65year-old woman was admitted to the emergency department with persistent typical chest pain after a fibrobronchoscopy. At the age of 30 she was diagnosed with chronic interstitial nephritis secondary to a familiar Alport Syndrome (AS), which was confirmed with renal biopsy. This primary renal involvement finally led her to chronic hemodialysis four years ago. She also had a history of hypertension, treated with angiotensin converting enzyme (ACE) inhibitors. (Source: International Journal of Cardiology)



Robotic Trans‐Abdominal Transplant Nephrectomy for a Failed Renal Allograft

Mon, 15 Sep 2014 00:00:00 +0100

Abstract Minimally invasive surgery for removal of a failed renal allograft has not previously been reported. Herein, we report the first robotic trans‐abdominal transplant nephrectomy (TN). A 34‐year‐old male with Alport's syndrome lost function of his deceased donor allograft after 12 years and presented with fever, pain over his allograft and hematuria. The operation was performed intra‐abdominally using the Da Vinci Robotic Surgical System with four trocars. The total operative time was 235 min and the estimated blood loss was less than 25 cm3. There were no peri‐operative complications observed and the patient was discharged to home less than 24 h postoperatively. The utilization of robotic technology facilitated the successful performance of a minimally invasive, tran...

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X-Linked Alport Syndrome Caused by Splicing Mutations in COL4A5.

Tue, 02 Sep 2014 00:00:00 +0100

CONCLUSIONS: This report highlights the importance of analyzing transcripts to enhance the mutation detection rate and provides insight into genotype-phenotype correlations. This approach can clarify the cause of atypically mild phenotypes in X-linked Alport syndrome. PMID: 25183659 [PubMed - as supplied by publisher] (Source: Clinical Journal of the American Society of Nephrology : CJASN)



Alport syndrome from bench to bedside: the potential of current treatment beyond RAAS blockade and the horizon of future therapies

Wed, 27 Aug 2014 00:00:00 +0100

The hereditary type IV collagen disease Alport syndrome (AS) always leads to end-stage renal failure. Yesterday, for the past 90 years, this course was described as ‘inevitable’. Today, RAAS blockade has changed the ‘inevitable’ course to a treatable disease. Tomorrow, researchers hope to erase the ‘always’ from ‘always leads to renal failure’ in the textbooks. This review elucidates therapeutic targets that evolve from research: (i) kidney embryogenesis and pathogenesis; (ii) phenotype-genotype correlation and the role of collagen receptors and podocytes; (iii) the malfunctioning Alport-GBM; (iv) tubulointerstitial fibrosis; (v) the role of proteinuria in pathogenesis and prognosis; and (vi) secondary events such as infections, hyperparathyr...



What Causes Proteinuria?

Mon, 18 Aug 2014 00:13:09 +0100

Discussion Proteinuria occurs relatively often in pediatric practice with 5-15% of school children having transient proteinuria, the most common cause. However, proteinuria can be a sign of kidney disease. Therefore, it is important to evaluate the proteinuria in light of the clinical situation. A good history and physical examination along with a full urinalysis and/or BUN and creatinine, or urine protein/creatinine ratio may be all that is necessary. Another patient with edema, hypertension or hematuria needs a fuller evaluation and treatment. Proteinuria is usually categorized into three groups to assist with evaluation and treatment and they include: transient, orthostatic or persistent. Transient means just that. It occurs only during the inciting problem and remits afterwards. It ge...



Alport syndrome: its effects on the glomerular filtration barrier and implications for future treatment.

Fri, 08 Aug 2014 00:00:00 +0100

This article is protected by copyright. All rights reserved. PMID: 25107927 [PubMed - as supplied by publisher] (Source: The Journal of Physiology)



Directed Differentiation of Pluripotent Stem Cells to Kidney Cells

Mon, 16 Jun 2014 00:00:00 +0100

Summary: Regenerative medicine affords a promising therapeutic strategy for the treatment of patients with chronic kidney disease. Nephron progenitor cell populations exist only during embryonic kidney development. Understanding the mechanisms by which these populations arise and differentiate is integral to the challenge of generating new nephrons for therapeutic purposes. Pluripotent stem cells (PSCs), comprising embryonic stem cells, and induced pluripotent stem cells (iPSCs) derived from adults, have the potential to generate functional kidney cells and tissue. Studies in mouse and human PSCs have identified specific approaches to the addition of growth factors, including Wnt and fibroblast growth factor, that can induce PSC differentiation into cells with phenotypic characteristics of...

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Renal histological features of school‐age children with asymptomatic haematuria and/or proteinuria: A multicenter study

Mon, 16 Jun 2014 00:00:00 +0100

ConclusionsOur findings indicate that IP and especially HP may have a high risk of development into CPG. IH, however, has a relatively low risk of severe histological lesions. Thus, IH per se might not be suggested as an indication for early renal biopsy. Long‐term follow‐up is necessary for these asymptomatic children. (Source: Nephrology)



Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY

Wed, 28 May 2014 00:00:00 +0100

We describe a novel mechanism of deletion‐induced Alu exonization, illustrating that deletions outside any transposed elements can activate splice sites within Alus and lead to new exon creation and genetic disease. Description of such events is underreported and is most useful for understanding how splice‐site sequences are recognized by the spliceosome machinery, as exemplified by a recent publication in Cell 152, 453–466, 2013. (Source: Molecular Genetics & Genomic Medicine)



Genetic diseases and molecular genetics

Wed, 21 May 2014 00:00:00 +0100

Conclusions: Our results strengthen the great significance of the heterozygous COL4A3/A4 mutations, not really well understood until after 1996, less than 20 years ago. These mutations are common, lead to TBMN and are the commonest cause of familial MH. More importantly however, these mutations lead much later in life to proteinuria, hypertension, CRF and ESKD and long term care is mandatory with prompt attention to the addition of proteinuria that requires urgent treatment. Heterozygous mutations COL4A3/A4 cause twice more patients to reach ESKD compared to classical XLAS and ARAS but fortunately at a much older age. Molecular genetics should be used more widely for an early diagnosis of this entity and more renal attention should be given to these patients to preserve kidney function and...



Acute kidney injury from multiple etiologies following kidney transplantation in a patient with alport syndrome

Mon, 14 Apr 2014 21:41:40 +0100

(Source: American Journal of Kidney Diseases)



De Novo Glomerular Diseases after Renal Transplantation.

Thu, 03 Apr 2014 00:00:00 +0100

Authors: Ponticelli C, Moroni G, Glassock RJ Abstract Glomerular diseases developing in the kidney allograft are more often recurrences of the original disease affecting the native kidneys. However, in an undefined number of cases de novo, glomerular diseases unrelated to the original disease in the native kidneys can develop in the transplanted kidney. The clinical presentation and histologic features of de novo diseases are often similar to those features observed in patients with primary or secondary GN in the native kidneys. However, in transplanted kidneys, the glomerular, vascular, and tubulointerstitial changes are often intertwined with structural abnormalities already present at the time of transplant or caused by antibody- or cell-mediated allograft rejection, immunosuppr...

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Renal histological features of school‐age children with asymptomatic hematuria and/or proteinuria: a multicenter study

Tue, 01 Apr 2014 00:00:00 +0100

ConclusionsOur findings indicate that IP and especially HP may have a high risk of development into CPG. IH, however, has a relatively low risk of severe histological lesions. Thus, IH per se might not be suggested as an indication for early renal biopsy. Long‐term follow‐up is necessary for these asymptomatic children. (Source: Nephrology)



Encapsulating peritoneal sclerosis in a patient with Alport's syndrome on long-term peritoneal dialysis.

Sat, 01 Mar 2014 00:00:00 +0100

Authors: Bahcebasi ZB, Akarsu O, Yildirim M, Kucuk H PMID: 24626018 [PubMed - in process] (Source: Saudi Journal of Kidney Diseases and Transplantation)



COL4A4-related nephropathy caused by a novel mutation in a large consanguineous Saudi family

Thu, 13 Feb 2014 15:03:38 +0100

Conclusion: Identification of the causative mutation is an efficient strategy for conclusive molecular diagnosis in the patients and to establish genotype/phenotype correlation. It is important to study and evaluate asymptomatic carriers, to predict prognosis of the disease and to obviate the need for another renal biopsy in at-risk related family members. While an accurate genetic diagnosis of AS provides valuable information for genetic counseling in the extended family members, it can also facilitate future prenatal diagnosis and planning for pre-implantation genetic diagnosis. (Source: International Journal of Pediatric Otorhinolaryngology)



Identification of a novel COL4A5 mutation in a Chinese family with X-linked Alport syndrome using exome sequencing.

Thu, 13 Feb 2014 00:00:00 +0100

Authors: Guo Y, Yuan J, Liang H, Xiao J, Xu H, Yuan L, Gao K, Wu B, Tang Y, Li X, Deng H Abstract Alport syndrome (AS) is an inherited disorder and clinically characterized by glomerulonephritis and end-stage kidney disease (ESRD). The aim of this study was to identify the gene responsible for glomerulopathy in a 4-generation Chinese pedigree. Exome sequencing was conducted in four patients of the family, and then direct sequencing was performed in other members of the pedigree. A novel missense mutation c.368G>A (p.Gly123Glu) in the collagen type IV alpha-5 gene (COL4A5) was found to be the genetic cause. The p.Gly123Glu mutation occurs prior to Gly-X-Y repeats in the alpha-5 chain of type IV collagen. Neither sensorineural hearing loss nor ocular abnormalities were present in ...



Collagen receptors integrin alpha2beta1 and discoidin domain receptor 1 regulate maturation of the glomerular basement membrane and loss of integrin alpha2beta1 delays kidney fibrosis in COL4A3 knockout mice.

Mon, 27 Jan 2014 00:00:00 +0100

In conclusion, the collagen receptors DDR1 and integrin α2β1 contribute to regulate GBM-maturation and to control matrix accumulation. As demonstrated in the type IV collagen disease Alport syndrome, glomerular cell-matrix interactions via collagen receptors play an important role in the progression of renal fibrosis. PMID: 24480069 [PubMed - as supplied by publisher] (Source: Matrix Biology)

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Skin Fibroblast Derived Inducible Pluripotent Stem Cells To Develop Disease In A Dish Model Of Alport's Disease

Sat, 11 Jan 2014 15:06:49 +0100

Alport's Syndrome is an inherited disease caused by mutations in COL4A3, COL4A4 and COL4A5 genes which code for type IV collagen α3, α4 and α5 chain genes, respectively. Approximately 85% of Alport's cases are X-linked dominant, caused by mutations in the COL4A5 gene. The disease is associated with glomerulonephritis, and hearing loss due to loss of basement membrane function. (Source: Journal of Surgical Research)



Molecular genetics of familial hematuric diseases

Fri, 29 Nov 2013 05:00:00 +0100

The familial hematuric diseases are a genetically heterogeneous group of monogenic conditions, caused by mutations in one of several genes. The major genes involved are the following: (i) the collagen IV genes COL4A3/A4/A5 that are expressed in the glomerular basement membranes (GBM) and are responsible for the most frequent forms of microscopic hematuria, namely Alport syndrome (X-linked or autosomal recessive) and thin basement membrane nephropathy (TBMN). (ii) The FN1 gene, expressed in the glomerulus and responsible for a rare form of glomerulopathy with fibronectin deposits (GFND). (iii) CFHR5 gene, a recently recognized regulator of the complement alternative pathway and mutated in a recently revisited form of inherited C3 glomerulonephritis (C3GN), characterized by isolated C3 depos...



Structure–function correlation of focal and diffuse temporal perifoveolar thinning in Alport syndrome

Wed, 23 Oct 2013 04:00:00 +0100

(Source: Clinical and Experimental Ophthalmology)



Deletion of the 5'exons of COL4A6 is not needed for the development of diffuse leiomyomatosis in patients with Alport syndrome

Fri, 18 Oct 2013 04:00:00 +0100

Conclusions These observations suggest that deletion of the 5' exons of COL4A6 and of the common promoter of the COL4A5 and COL4A6 genes is not essential for the development of leiomyomatosis in patients with ATS, and that COL4A5_COL4A6 deletions extending into COL4A6 exon 3 may not result in ATS-DL. (Source: Journal of Medical Genetics)



Clear lens phacoemulsification in Alport syndrome: refractive results and electron microscopic analysis of the anterior lens capsule.

Wed, 16 Oct 2013 04:00:00 +0100

Conclusions: Clear lens phacoemulsification and foldable intraocular lens implantation is a safe and effective therapeutic choice for the management of uncorrectable refractive errors and low visual acuity due to anterior lenticonus in patients with Alport syndrome.

PMID: 24170525 [PubMed - as supplied by publisher] (Source: European Journal of Ophthalmology)

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Identification and characterization of a defect CYP3A4 genotype in a kidney transplant patient with severely diminished tacrolimus clearance.

Mon, 14 Oct 2013 04:00:00 +0100

We report on a 19-year-old kidney-transplanted patient suffering from Alport syndrome, who experienced unexpected high tacrolimus plasma trough levels during immunosuppressant therapy. Since non-adherence, liver failure or drug-interactions could be excluded we hypothesized a diminished metabolism of the drug caused by mutations in the main detoxification enzyme CYP3A4. Exome sequencing revealed a novel SNP (c.802C>T) resulting in a premature stop codon in CYP3A4 exon 5. Accordingly, no CYP3A4 protein could be detected in a kidney biopsy tissue and there was lack of expression in HepG2 cells, transiently transfected with the mutated CYP3A4. Additionally, the patient harboured inactive CYP3A5*3, resulting in loss of function of the entire CYP3A locus explaining the deteriorated tacrolimu...



Nanoscale protein architecture of the kidney glomerular basement membrane

Tue, 08 Oct 2013 00:00:00 +0100

In multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction microscopy (STORM) to resolve the in situ molecular organization of proteins within the kidney glomerular basement membrane (GBM), an essential mediator of glomerular ultrafiltration. Using multichannel STORM and STORM-electron microscopy correlation, we constructed a molecular reference frame that revealed a laminar organization of ECM proteins within the GBM. Separate analyses of domains near the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM revealed a highly orie...



Structure‐function correlation of focal and diffuse temporal perifoveolar thinning in Alport syndrome

Mon, 30 Sep 2013 04:00:00 +0100

(Source: Clinical and Experimental Ophthalmology)



Repeatability and sensitivity of high resolution blood volume mapping in mouse kidney disease

Wed, 04 Sep 2013 04:00:00 +0100

ConclusionIn vivo renal iron‐oxide–based RBV mapping in mice complements the physiological information obtained from conventional assays of kidney function and could shed new insights into the pathological mechanisms of kidney disease. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc. (Source: Journal of Magnetic Resonance Imaging)