1,285 results match your criteria Alport Syndrome


Alport syndrome: deducing the mode of inheritance from the presence of haematuria in family members.

Authors:
Judy Savige

Pediatr Nephrol 2018 Nov 30. Epub 2018 Nov 30.

Department of Medicine, Melbourne Health and Northern Health, The University of Melbourne, Parkville, 3050, Australia.

The diagnosis of Alport syndrome is suspected when an individual has haematuria or renal failure, together with a hearing loss; haematuria or renal failure, and a family history of Alport syndrome; or a pathognomonic Alport feature, such as lenticonus, fleck retinopathy, a lamellated glomerular basement membrane (GBM), or a GBM that lacks the collagen IV α3α4α5 network. The diagnosis of Alport syndrome is optimally confirmed by the demonstration of a mutation in the COL4A5 gene or two mutations in trans in the COL4A3 or COL4A4 genes. In practice, genetic testing for Alport syndrome is not widely available, and even with testing, causative mutations are not demonstrated in 5% of cases. Read More

View Article
November 2018

Establishment of microRNA, transcript and protein regulatory networks in Alport syndrome induced pluripotent stem cells.

Mol Med Rep 2018 Nov 20. Epub 2018 Nov 20.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

Alport syndrome (AS) is an inherited progressive disease caused by mutations in genes encoding for the α3, α4 and α5 chains, which are an essential component of type IV collagen and are required for formation of the glomerular basement membrane. However, the underlying etiology of AS remains largely unknown, and the aim of the present study was to examine the genetic mechanisms in AS. Induced pluripotent stem cells (iPSCs) were generated from renal tubular cells. Read More

View Article
November 2018

De novo mutations in COL4A5 identified by whole exome sequencing in two girls with Alport syndrome in Korea.

Korean J Pediatr 2018 Nov 26. Epub 2018 Nov 26.

Green Cross Genome, Yongin, Korea, Gyeonggi-do, Korea.

Alport syndrome (ATS) is an inherited glomerular disease caused by mutations in one of the type IV collagen novel chains (α3, α4, and α5). ATS is characterized by persistent microscopic hematuria starting from infancy, eventually leading to either progressive nephritis or end-stage renal disease. There are three known genetic forms of ATS, i. Read More

View Article
November 2018
2 Reads

MYH9 Associated nephropathy.

Nefrologia 2018 Nov 21. Epub 2018 Nov 21.

Enfermedades Renales Hereditarias, Servicio de Nefrología, Fundació Puigvert, Barcelona, España; Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, España; Universidad Autònoma de Barcelona, REDinREN, Instituto de Investigación Carlos III, Barcelona, España. Electronic address:

MYH9 related diseases are caused by mutations in the MYH9 gene and constitute a rare group of genetic entities. Its inheritance follows an autosomal dominant pattern. The MYH9 gene, encodes the nonmuscle myosin heavy chain IIA, expressed in different tissues and especially in podocytes and mesangial cells. Read More

View Article
November 2018
1 Read

The utility of urinary CD80 as a diagnostic marker in patients with renal diseases.

Sci Rep 2018 Nov 23;8(1):17322. Epub 2018 Nov 23.

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.

CD80, which regulates T cell activation, may provide a differential diagnostic marker between minimal change disease (MCD) and other renal diseases, including focal segmental glomerular sclerosis (FSGS). However, recent reports show contrasting results. Therefore, we evaluated the utility of urinary CD80 as a diagnostic biomarker. Read More

View Article
November 2018
4 Reads

DNA-encoded library-derived DDR1 inhibitor prevents fibrosis and renal function loss in a genetic mouse model of Alport syndrome.

ACS Chem Biol 2018 Nov 19. Epub 2018 Nov 19.

The importance of DDR1 in renal fibrosis has been shown via gene knockout and use of antisense oligonucleotides; however, these techniques act via a reduction of DDR1 protein while we prove the therapeutic potential of inhibiting DDR1 phosphorylation with a small molecule. To date, efforts to generate a selective small-molecule to specifically modulate the activity of DDR1 in an in vivo model have been unsuccessful. We performed parallel DNA encoded library screens against DDR1 and DDR2, and discovered a chemical series that is highly selective for DDR1 over DDR2. Read More

View Article
November 2018
13 Reads

Should We Diagnose Autosomal Dominant Alport Syndrome When There Is a Pathogenic Heterozygous or Variant?

Authors:
Judy Savige

Kidney Int Rep 2018 Nov 22;3(6):1239-1241. Epub 2018 Aug 22.

Department of Medicine (Melbourne Health) and Northern Health, The University of Melbourne, Parkville, Victoria, Australia.

View Article
November 2018

Renal transplantation in patients with Alport syndrome: patient selection, outcomes, and donor evaluation.

Int J Nephrol Renovasc Dis 2018 16;11:267-270. Epub 2018 Oct 16.

Division of Nephrology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55454, USA,

Alport syndrome is an inherited disorder of basement membrane collagen IV that frequently results in end-stage renal disease. Patients with Alport syndrome who undergo renal transplantation have generally excellent outcomes. Posttransplant antiglomerular basement membrane nephritis is a rare complication of renal transplantation for Alport syndrome. Read More

View Article
October 2018
4 Reads

Abnormal Expression of miR-21 in Kidney Tissue of Dogs With X-Linked Hereditary Nephropathy: A Canine Model of Chronic Kidney Disease.

Vet Pathol 2018 Oct 28:300985818806050. Epub 2018 Oct 28.

2 Sanofi, Framingham, MA, USA.

MicroRNAs (miRNAs) are a group of small noncoding RNAs that act as regulators of posttranslational gene/protein expression and are known to play a key role in physiological and pathological processes. The objective of our study was to compare expression of miR-21 in renal tissue from dogs affected with chronic kidney disease (CKD) caused by X-linked hereditary nephropathy (XLHN), a disease equivalent to human Alport syndrome, to that from unaffected dogs. Additionally, we sought to characterize changes in relative mRNA expression of various genes associated with miR-21 function. Read More

View Article
October 2018
13 Reads

Identification of genetic causes for sporadic steroid-resistant nephrotic syndrome in adults.

Kidney Int 2018 Nov;94(5):1013-1022

Inserm U1163, Imagine Institute, Paris Descartes University, Paris, France; Adult Nephrology & Transplantation, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte, Necker Hospital, Paris, France. Electronic address:

Monogenic forms of Steroid-Resistant Nephrotic Syndrome (SRNS) have been widely characterized, but genetic screening paradigms preferentially address congenital, infantile onset, and familial cases. Our aim was to characterize the distribution of disease-causing gene mutations in adults with sporadic SRNS or focal segmental glomerulosclerosis (FSGS). We selected adult patients with non-syndromic, biopsy-proven FSGS or SRNS in the absence of known family history. Read More

View Article
November 2018
4 Reads

[Diffuse esophageal leiomyomatosis and Alport's syndrome: A case report and review of the literature].

Ann Pathol 2018 Oct 12. Epub 2018 Oct 12.

Service d'anatomie et cytologie pathologiques, hôpital Nord, chemin des Bourrely, 13015 Marseille, France; U1068-CRCM, Aix Marseille université, 13015 Marseille, France.

Diffuse esophageal leiomyomatosis is a rare esophageal tumor characterized by circumferential thickening of smooth muscle layers. Diffuse esophageal leiomyomatosis can be associated with Alport's syndrome and therefore diagnosed by skin biopsy. Alport syndrome is a hereditary disease usually defined by the association of glomerular nephropathy and perceptual deafness. Read More

View Article
October 2018
2 Reads

Focal Degeneration of Vestibular Neuroepithelium in the Cristae Ampullares of Three Human Subjects.

Otol Neurotol 2018 Dec;39(10):e1100-e1110

Otopathology Laboratory, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary.

Background: We report a unique pattern of focal degeneration of the neuroepithelium of cristae ampullares, thick subepithelial extracellular deposits, and neural degeneration in three humans.

Objective: To characterize the pattern of vestibular degeneration and measure the thickness of subepithelial deposits in these three cases and controls.

Methods: The subepithelial deposits of vestibular end organs in three subject cases and controls were studied using hematoxylin and eosin, periotic acid-Schiff, Gomori trichrome staining, and immunostaining for antineurofilament, antimyosin VIIa, and anticollagen 4a1. Read More

View Article
December 2018
1 Read

Hydroxypropyl-β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis.

Kidney Int 2018 Dec 6;94(6):1151-1159. Epub 2018 Oct 6.

Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA; Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address:

Studies suggest that altered renal lipid metabolism plays a role in the pathogenesis of diabetic kidney disease and that genetic or pharmacological induction of cholesterol efflux protects from the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether altered lipid metabolism contributes to renal failure in the Col4a3 knockout mouse model for Alport Syndrome. There was an eight-fold increase in the cholesterol content in renal cortexes of mice with Alport Syndrome. Read More

View Article
December 2018
1 Read

Panel sequencing distinguishes monogenic forms of nephritis from nephrosis in children.

Nephrol Dial Transplant 2018 Mar 21. Epub 2018 Mar 21.

Department of Medicine, Division of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Alport syndrome (AS) and atypical hemolytic-uremic syndrome (aHUS) are rare forms of chronic kidney disease (CKD) that can lead to a severe decline of renal function. Steroid-resistant nephrotic syndrome (SRNS) is more common than AS and aHUS and causes 10% of childhood-onset CKD. In recent years, multiple monogenic causes of AS, aHUS and SRNS have been identified, but their relative prevalence has yet to be studied together in a typical pediatric cohort of children with proteinuria and hematuria. Read More

View Article
March 2018
6 Reads

A family case of X-linked Alport syndrome patients with a novel variant in COL4A5.

CEN Case Rep 2018 Oct 6. Epub 2018 Oct 6.

Department of Pediatrics, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, Japan.

We herein report 2 Japanese patients with X-linked Alport syndrome (XLAS), with a novel variant in COL4A5. Patient 1 was a 16-year-old Japanese girl with a history of microscopic hematuria, without proteinuria, renal dysfunction, deafness, or ocular abnormalities. At 13 years of age, renal biopsy was performed; however, a diagnosis of AS was not considered. Read More

View Article
October 2018
6 Reads

Does Religion Predict Health-Promoting Behaviors in Community-Dwelling Elderly People?

J Relig Health 2018 Oct 5. Epub 2018 Oct 5.

Midwifery Department, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

As the aging phenomenon gains importance in many societies, regular health-promoting activities by the elderlies become more crucial for disability reduction and their health promotion. Religious viewpoints and perspectives can have an influence on the individuals' assessment of life events. Recent studies show a correlation between religiosity and mental health. Read More

View Article
October 2018
10 Reads

Long-term survival in Japanese renal transplant recipients with Alport syndrome: a retrospective study.

BMC Nephrol 2018 Oct 3;19(1):249. Epub 2018 Oct 3.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Background: Patients with Alport syndrome (AS) develop progressive kidney dysfunction due to a hereditary type IV collagen deficiency. Survival of the kidney allograft in patients with AS is reportedly excellent because AS does not recur. However, several studies have implied that the type IV collagen in the GBM originates from podocytes recruited from the recipient's bone marrow-derived cells, suggesting the possibility of AS recurrence. Read More

View Article
October 2018
2 Reads
1.520 Impact Factor

Peroral Endoscopic Myotomy in Diffuse Thickened Esophageal Wall in an Adolescent.

Case Rep Gastroenterol 2018 May-Aug;12(2):497-503. Epub 2018 Aug 23.

Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.

Achalasia is an extremely rare pathology in children. Peroral endoscopic myotomy (POEM) is the gold standard for the surgical treatment of achalasia in adults, but only a limited number of cases of achalasia treatment using POEM in children have been published in the literature. Sometimes, high-resolution manometry signs of achalasia can mimic diffuse esophageal leiomyoma. Read More

View Article
August 2018
2 Reads

[X-linked Alport syndrome: auditory pathogenic variant features and further genotype-phenotype correlations in female patients].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018 Aug;32(16):1232-1237

Department of Pediatrics, Peking University First Hospital.

To analyze the audiological characteristics of female patients with X-linked Alport syndrome and to explore the relationship between genotype and phenotype in China. The hearing data of 64 females diagnosed as Alport syndrome was reviewed and analyzed. All coding exons of COL4A5 genes were PCR-amplified and sequenced with genomic DNA, or mRNA of COL4A5 gene was RT-PCR amplified and sequenced with skin fibroblast. Read More

View Article
August 2018
1 Read

Diagnosing Alport Syndrome: Lessons from the Pediatric Ward.

Nephron 2018 13;140(3):203-210. Epub 2018 Sep 13.

Department of Pediatric Nephrology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.

Background: Alport syndrome is a rare inheritable kidney disease frequently leading to end-stage kidney disease in young adults. Patients could benefit from early recognition of the disease. In several children with Alport syndrome, a parent was noticed to have renal symptoms attributed to another renal disease. Read More

View Article
September 2018
2 Reads

A Clinical Study of Effect of Hyperpyrexia on Otoacoustic Emissions in Children.

Indian J Otolaryngol Head Neck Surg 2018 Sep 26;70(3):438-449. Epub 2018 Apr 26.

Department of ENT, PES Institute of Medical Science and Research, Kuppam, 517 425 India.

Various degrees of sensory neural hearing loss can be seen in the progression of some hereditary periodic fever syndromes. Otoacoustic emission testing can help to establish the inner ear involvement at an early period of a periodic fever with a risk of hearing loss (Abdul Kadir et al. in J Int Adv Otol 9(2. Read More

View Article
September 2018
11 Reads

INNER MACULAR CHANGES AFTER VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING FOR RHEGMATOGENOUS RETINAL DETACHMENT: Similarity With Alport Syndrome.

Retina 2018 Sep 7. Epub 2018 Sep 7.

Department of Ophthalmology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.

Purpose: The internal limiting membrane (ILM), the innermost basement membrane of the retina, is peeled occasionally during vitreous surgery. This study aimed to investigate the effect of ILM loss on the retina.

Methods: We used optical coherence tomography to retrospectively evaluate retinal changes in 26 eyes (11 ILM-peeled and 15 ILM-unpeeled eyes) of 26 patients after vitrectomy for retinal detachment. Read More

View Article
September 2018
1 Read

Temporal Bone Histopathology of X-linked Inherited Alport Syndrome.

Laryngoscope Investig Otolaryngol 2018 Aug 9;3(4):311-314. Epub 2018 Aug 9.

Department of Otolaryngology Massachusetts Eye and Ear Infirmary Boston Massachusetts U.S.A.

Objective: To describe the histopathologic findings within the human cochlea in X-linked Alport syndrome.

Study Design: Histopathologic analysis of cellular elements within the human cochlea by light microscopy.

Materials And Methods: A right and a left cochleae of a man with genetically confirmed X-linked Alport syndrome was studied post-mortem. Read More

View Article
August 2018
4 Reads

Systemic Activation of Activin A Signaling Causes Chronic Kidney Disease-Mineral Bone Disorder.

Int J Mol Sci 2018 Aug 23;19(9). Epub 2018 Aug 23.

Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.

The high cardiovascular mortality associated with chronic kidney disease (CKD) is caused in part by the CKD-mineral bone disorder (CKD-MBD) syndrome. The CKD-MBD consists of skeletal, vascular and cardiac pathology caused by metabolic derangements produced by kidney disease. The prevalence of osteopenia/osteoporosis resulting from the skeletal component of the CKD-MBD, renal osteodystrophy (ROD), in patients with CKD exceeds that of the general population and is a major public health concern. Read More

View Article
August 2018
6 Reads

A review of clinical characteristics and genetic backgrounds in Alport syndrome.

Clin Exp Nephrol 2018 Aug 20. Epub 2018 Aug 20.

Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Read More

View Article
August 2018
19 Reads

Anterior lenticonus associated with Alport syndrome.

Indian J Ophthalmol 2018 09;66(9):1330-1331

Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

View Article
September 2018
2 Reads
0.930 Impact Factor

It is an Alport syndrome, not a simple hypertensive retinopathy.

Indian J Ophthalmol 2018 09;66(9):1319-1321

Department of Retina, Anand Eye Institute, Hyderabad, Telangana, India.

View Article
September 2018
7 Reads

Induced Pluripotent Stem Cell-Derived Podocyte-Like Cells as Models for Assessing Mechanisms Underlying Heritable Disease Phenotype: Initial Studies Using Two Alport Syndrome Patient Lines Indicate Impaired Potassium Channel Activity.

J Pharmacol Exp Ther 2018 Nov 13;367(2):335-347. Epub 2018 Aug 13.

Monash Institute of Pharmaceutical Sciences (J.M.H., J.N.S., T.H.V., I.P.L.A., J.K.H., W.-L.L., K.L.) and Department of Anatomy and Developmental Biology (S.S., C.L.F., S.D.R.), Monash University, Victoria, Australia; and Department of Medicine, Royal Melbourne Hospital, Victoria, Australia (J.S.).

Renal podocyte survival depends upon the dynamic regulation of a complex cell architecture that links the glomerular basement membrane to integrins, ion channels, and receptors. Alport syndrome is a heritable chronic kidney disease where mutations in 3, 4, or 5 collagen genes promote podocyte death. In rodent models of renal failure, activation of the calcium-sensing receptor (CaSR) can protect podocytes from stress-related death. Read More

View Article
November 2018
22 Reads

Endoplasmic reticulum stress and monogenic kidney diseases in precision nephrology.

Pediatr Nephrol 2018 Aug 11. Epub 2018 Aug 11.

Division of Nephrology, Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8126, St. Louis, MO, 63110, USA.

The advent of next-generation sequencing (NGS) in recent years has led to a rapid discovery of novel or rare genetic variants in human kidney cell genes, which is transforming the risk assessment, diagnosis, and treatment of kidney disease. Mutations may lead to protein misfolding, disruption of protein trafficking, and endoplasmic reticulum (ER) retention. An imbalance between the load of misfolded proteins and the folding capacity of the ER causes ER stress and unfolded protein response. Read More

View Article
August 2018
1 Read

Germline mosaicism is a pitfall in the diagnosis of "sporadic" X-linked Alport syndrome.

J Nephrol 2018 Jul 30. Epub 2018 Jul 30.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo, Hokkaido, 060-8638, Japan.

Approximately 80% of patients with Alport syndrome have X-linked Alport syndrome (XLAS), which is caused by mutations in the type IV collagen alpha 5 gene (COL4A5). In patients with XLAS, approximately 10-15% of COL4A5 mutations occur as spontaneous events. Here, we describe maternal germline mosaicism in a family of XLAS patients. Read More

View Article
July 2018
2 Reads

Novel variants in and are rare causes of FSGS in two unrelated families.

Hum Genome Var 2018 10;5:15. Epub 2018 Jul 10.

2Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224 USA.

We report two female patients with focal segmental glomerulosclerosis and chronic kidney disease. The first patient was found to have a heterozygous, de novo, pathogenic variant in (c.141+1G>A, IVS2+1G>A), which is associated with Alport syndrome. Read More

View Article
July 2018
6 Reads

Expert consensus guidelines for the genetic diagnosis of Alport syndrome.

Pediatr Nephrol 2018 Jul 9. Epub 2018 Jul 9.

Genetics, Guy's Hospital, Viapath, London, UK.

Recent expert guidelines recommend genetic testing for the diagnosis of Alport syndrome. Here, we describe current best practice and likely future developments. In individuals with suspected Alport syndrome, all three COL4A5, COL4A3 and COL4A4 genes should be examined for pathogenic variants, probably by high throughput-targeted next generation sequencing (NGS) technologies, with a customised panel for simultaneous testing of the three Alport genes. Read More

View Article
July 2018
10 Reads

Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport Syndrome.

J Am Soc Nephrol 2018 Aug 29;29(8):2244-2254. Epub 2018 Jun 29.

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS. Read More

View Article
August 2018
10 Reads

Urinary epidermal growth factor as a prognostic marker for the progression of Alport syndrome in children.

Pediatr Nephrol 2018 Oct 11;33(10):1731-1739. Epub 2018 Jun 11.

Department of Pediatrics, Peking University First Hospital, No.1 Xi An Men Da Jie, Beijing, 100034, People's Republic of China.

Background: Alport syndrome is a rare hereditary kidney disease manifested with progressive renal failure. Considerable variation exists in terms of disease progression among patients with Alport syndrome. Identification of patients at high risk of rapid progression remains an unmet need. Read More

View Article
October 2018
9 Reads

Heterozygous Variants in Histologically Diagnosed Focal Segmental Glomerulosclerosis.

Front Pediatr 2018 12;6:171. Epub 2018 Jun 12.

Institute of Human Genetics, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

Steroid-resistant nephrotic syndrome (SRNS) is one of the most frequent causes for chronic kidney disease in childhood. In ~30% of these cases a genetic cause can be identified. The histological finding in SRNS is often focal segmental glomerulosclerosis (FSGS). Read More

View Article
June 2018
4 Reads

Speech, language, and hearing function in twins with Alport syndrome: A seven-year retrospective case report.

J Otol 2017 Jun 21;12(2):86-96. Epub 2017 Mar 21.

Department of Communication Sciences and Disorders, Oklahoma State University, United States.

Alport syndrome is an X-linked syndrome that results in nephritis, renal failure, sensorineural hearing loss, and eye deficits. As a result of sensorineural hearing loss, these individuals are likely to experience difficulties in the area of speech and language. While studies in the past have examined the speech and language characteristics of children with syndromic sensorineural hearing loss, to our knowledge there are no previous studies to have documented the speech and language characteristics of these children on a long-term basis. Read More

View Article
June 2017
2 Reads

Bilateral giant macular holes: A rare manifestation of Alport syndrome.

Eur J Ophthalmol 2018 May 1:1120672118781232. Epub 2018 May 1.

1 Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal.

Purpose: Alport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations. Herein, we present a rare case of a patient diagnosed with Alport syndrome and bilateral giant macular holes.

Case Description: A 40-year-old woman with a previously unreported mutation in the COL4A4 gene suggestive of autosomal-recessive Alport syndrome presented at our department. Read More

View Article
May 2018
3 Reads

Genotype and Outcome After Kidney Transplantation in Alport Syndrome.

Kidney Int Rep 2018 May 2;3(3):652-660. Epub 2018 Feb 2.

Division of Nephrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Introduction: Alport syndrome (AS) is caused by mutations in α3/α4/α5 (IV) collagen genes, the severity of which determine the progression of AS. Posttransplantation outcome is good, although anti-glomerular basement membrane (anti-GBM) glomerulonephritis occurs in 3% to 5% of recipients, clustering in patients with a severe mutation. We assessed whether the severity of the underlying AS mutation affects graft and patients outcome after transplantation, including the occurrence of anti-GBM nephritis. Read More

View Article
May 2018
27 Reads

A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases.

Kidney Int 2018 Aug 22;94(2):363-371. Epub 2018 May 22.

Molecular Biology Laboratory, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autònoma de Barcelona, Red de Investigación Renal (REDINREN), Instituto de Investigación Carlos III, Barcelona, Catalonia, Spain; Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autònoma de Barcelona, REDinREN, Instituto de Investigación Carlos III, Barcelona, Catalonia, Spain. Electronic address:

Molecular diagnosis of inherited kidney diseases remains a challenge due to their expanding phenotypic spectra as well as the constantly growing list of disease-causing genes. Here we develop a comprehensive approach for genetic diagnosis of inherited cystic and glomerular nephropathies. Targeted next generation sequencing of 140 genes causative of or associated with cystic or glomerular nephropathies was performed in 421 patients, a validation cohort of 116 patients with previously known mutations, and a diagnostic cohort of 207 patients with suspected inherited cystic disease and 98 patients with glomerular disease. Read More

View Article
August 2018
3 Reads

Shining a Light on Alport Syndrome.

Cell Chem Biol 2018 May;25(5):497-498

Murdoch Children's Research Institute, Flemington Rd., Parkville, VIC 3052, Australia; Department of Pediatrics, The University of Melbourne, Parkville, VIC 3010, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address:

In this issue of Cell Chemical Biology, Omachi et al. (2018) present a split Nanoluciferase system to identify successful protein trimerization in Alport syndrome. This elegant proof of concept suggests opportunities for drug screening for Alport syndrome and may be transferable to the study of other diseases affecting protein-protein interactions. Read More

View Article
May 2018
3 Reads

COL4A5 and LAMA5 variants co-inherited in familial hematuria: digenic inheritance or genetic modifier effect?

BMC Nephrol 2018 May 16;19(1):114. Epub 2018 May 16.

Molecular Medicine Research Center, Department of Biological Sciences, University of Cyprus, 1, University Avenue, 2109, Nicosia, Cyprus.

Background: About 40-50% of patients with familial microscopic hematuria (FMH) caused by thin basement membrane nephropathy (TBMN) inherit heterozygous mutations in collagen IV genes (COL4A3, COL4A4). On long follow-up, the full phenotypic spectrum of these patients varies a lot, ranging from isolated MH or MH plus low-grade proteinuria to chronic renal failure of variable degree, including end-stage renal disease (ESRD).

Methods: Here, we performed Whole Exome Sequencing (WES) in patients of six families, presenting with autosomal dominant FMH, with or without progression to proteinuria and loss of renal function, all previously found negative for severe collagen IV mutations. Read More

View Article
May 2018
3 Reads
1.520 Impact Factor

Lysyl oxidase like-2 contributes to renal fibrosis in Col4α3/Alport mice.

Kidney Int 2018 Aug 16;94(2):303-314. Epub 2018 May 16.

PharmAkea Inc., San Diego, California, USA.

Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lung fibrosis, little is known regarding its role in renal fibrosis. Read More

View Article
August 2018
2 Reads

The COL4A3 and COL4A4 Digenic Mutations in cis Result in Benign Familial Hematuria in a Large Chinese Family.

Cytogenet Genome Res 2018 9;154(3):132-136. Epub 2018 May 9.

Mutations in the COL4A5 gene result in X-linked Alport syndrome, homozygous or compound heterozygous mutations in COL4A3 or COL4A4 are responsible for autosomal recessive Alport syndrome, and heterozygous mutations in COL4A3 or COL4A4 cause autosomal dominant Alport syndrome or benign familial hematuria. Recently, the existence of a digenic inheritance in Alport syndrome has been demonstrated. We here report heterozygous COL4A3 and COL4A4 digenic mutations in cis responsible for benign familial hematuria. Read More

View Article
June 2018
2 Reads

Clinical Outcomes of Kidney Transplantation in Patients With Biopsy-Proven Glomerulonephritis.

Transplant Proc 2018 May;50(4):1009-1012

Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea; Keimyung University Kidney Institute, Daegu, Korea. Electronic address:

Background: The clinical outcomes after kidney transplantation (KT) according to the types of glomerulonephritis (GN) as the cause of end-stage renal disease (ESRD) are various, but there are not many studies on this.

Methods: Among 1,253 patients who had KT between November 1982 and January 2017, 183 recipients with biopsy-proven GN as the primary cause of ESRD were enrolled. We analyzed the incidence of recurrent GN and the factors associated with recurrence and graft and patient survivals. Read More

View Article
May 2018
5 Reads

Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane.

Matrix Biol 2018 Oct 16;71-72:250-261. Epub 2018 Apr 16.

Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Read More

View Article
October 2018
1 Read

Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes.

Cytogenet Genome Res 2018 15;154(1):30-36. Epub 2018 Feb 15.

Institute of Clinical Laboratory Science, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p. Read More

View Article
April 2018
2 Reads

The 6th Rare Disease South Eastern Europe (See) Meeting, Skopje, Macedonia (November 11th, 2017).

Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2017 Dec;38(3):163-168

Macedonian Academy of Science and Arts, Skopje, Republic of Macedonia.

The sixth SEE meeting on rare diseases (RDs) was held in MASA the November 10th, 2017. A block of lectures on rare renal diseases started the meeting: nephrotic syndrome, Alport syndrome, atypical HUS, hypophosphatemic rickets, CAKUT were presented in all complexities. Their molecular and genetic mechanisms were discussed. Read More

View Article
December 2017
2 Reads

Osteopontin drives renal metabolic dysfunction in Alport syndrome.

Authors:
Ellen F Carney

Nat Rev Nephrol 2018 Jun;14(6):354

Nature Reviews Nephrology, .

View Article
June 2018
3 Reads

Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits.

JCI Insight 2018 Mar 22;3(6). Epub 2018 Mar 22.

Interdisciplinary Stem Cell Institute.

Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. Read More

View Article
March 2018
5 Reads

Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group.

Kidney Int 2018 05 16;93(5):1045-1051. Epub 2018 Mar 16.

Clinic of Nephrology and Rheumatology, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany.

Mutations in the genes COL4A3, COL4A4, and COL4A5 affect the synthesis, assembly, deposition, or function of the collagen IV α345 molecule, the major collagenous constituent of the mature mammalian glomerular basement membrane. These mutations are associated with a spectrum of nephropathy, from microscopic hematuria to progressive renal disease leading to ESRD, and with extrarenal manifestations such as sensorineural deafness and ocular anomalies. The existing nomenclature for these conditions is confusing and can delay institution of appropriate nephroprotective therapy. Read More

View Article
May 2018
14 Reads