2,552 results match your criteria Alport Syndrome


Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5.

Nat Commun 2020 Jun 2;11(1):2777. Epub 2020 Jun 2.

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

Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report the development of an exon-skipping therapy using an antisense-oligonucleotide (ASO) for severe male X-linked Alport syndrome (XLAS). We targeted truncating variants in exon 21 of the COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, and in vitro and in vivo treatment efficacy evaluation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-16605-xDOI Listing

Glomerular filtration and podocyte tensional homeostasis: importance of the minor type IV collagen network.

Biomech Model Mechanobiol 2020 May 27. Epub 2020 May 27.

Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church St SE, Minneapolis, MN, 55455, USA.

The minor type IV collagen chain, which is a significant component of the glomerular basement membrane in healthy individuals, is known to assemble into large structures (supercoils) that may contribute to the mechanical stability of the collagen network and the glomerular basement membrane as a whole. The absence of the minor chain, as in Alport syndrome, leads to glomerular capillary demise and eventually to kidney failure. An important consideration in this problem is that the glomerular capillary wall must be strong enough to withstand the filtration pressure and porous enough to permit filtration at reasonable pressures. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10237-020-01347-yDOI Listing

A deletion in the N-terminal polymerizing domain of laminin β2 is a new mouse model of chronic nephrotic syndrome.

Kidney Int 2020 Feb 20. Epub 2020 Feb 20.

Department of Internal Medicine, Division of Nephrology, Washington University, St. Louis, Missouri, USA. Electronic address:

The importance of the glomerular basement membrane (GBM) in glomerular filtration is underscored by the manifestations of Alport and Pierson syndromes, caused by defects in type IV collagen α3α4α5 and the laminin β2 chain, respectively. Lamb2 null mice, which model the most severe form of Pierson syndrome, exhibit proteinuria prior to podocyte foot process effacement and are therefore useful for studying GBM permselectivity. We hypothesize that some LAMB2 missense mutations that cause mild forms of Pierson syndrome induce GBM destabilization with delayed effects on podocytes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.01.033DOI Listing
February 2020

Long-term ACE inhibition in Alport syndrome: are the benefits worth the risks?

Kidney Int 2020 Jun;97(6):1104-1106

Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.

Gross et al. present results of the EARLY PRO-TECT trial, a randomized controlled trial of ramipril versus placebo in children with early-stage Alport syndrome. Although under-enrolled and not a positive trial in the traditional sense, EARLY PRO-TECT does provide strong supportive evidence for both long-term safety and a clinical benefit of early treatment with angiotensin-converting enzyme inhibitors in slowing the progression of both albuminuria and estimated glomerular filtration rate decline in children with Alport syndrome. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.01.030DOI Listing

Generation of an induced pluripotent stem cell line (SHCDNRi001-A) from a patient with X-linked Alport syndrome carrying a heterozygous p.G409S (c. 1225 G > A) mutation in the COL4A5 gene.

Stem Cell Res 2020 May 6;45:101833. Epub 2020 May 6.

Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai 200062, China. Electronic address:

X-linked Alport syndrome (XLAS) is a rare form of hereditary nephritis caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain. A skin biopsy was performed on one female patient with XLAS who carried a heterozygous p.G409S (c. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scr.2020.101833DOI Listing

Trimerization and Genotype-Phenotype Correlation of Mutants in Alport Syndrome.

Kidney Int Rep 2020 May 30;5(5):718-726. Epub 2020 Jan 30.

Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.

Introduction: Alport syndrome is a hereditary glomerulonephritis that results from the disruption of collagen α345(IV) heterotrimerization caused by mutation in , or genes. Many clinical studies have elucidated the correlation between genotype and phenotype, but there is still much ambiguity and insufficiency. Here, we focused on the α345(IV) heterotrimerization of α5(IV) missense mutant as a novel factor to further understand the pathophysiology of Alport syndrome. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2020.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210609PMC

COL4A3 mutation is an independent risk factor for poor prognosis in children with Alport syndrome.

Pediatr Nephrol 2020 May 11. Epub 2020 May 11.

Division of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, 06230, Ankara, Turkey.

Background: Alport syndrome (AS) is an inherited glomerular disease caused by mutations in COL4A3, COL4A4, or COL4A5. Associations between clinical manifestations and genotype are not yet well defined. Our study aimed to define clinical and genetic characteristics, establish genotype-phenotype correlations, and determine prognosis of AS in children. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04574-8DOI Listing

IgA Nephropathy Concomitant With Karyomegalic Interstitial Nephritis.

Am J Med Sci 2020 Apr 17. Epub 2020 Apr 17.

Department of Renal Pathology, King Medical Diagnostics Center, Guangzhou, China.

Immunoglobulin A (IgA) nephropathy is one of the most common glomerulonephritis characterized by the deposition of IgA in glomerular mesangium. Karyomegalic interstitial nephritis (KIN) is a rare interstitial nephritis with potential hereditary factors. IgA nephropathy concomitant with KIN has not yet been reported. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjms.2020.04.010DOI Listing

Clinical trial recommendations for potential Alport syndrome therapies.

Kidney Int 2020 Jun 6;97(6):1109-1116. Epub 2020 Apr 6.

Department of Nephrology and Hypertension, The Cleveland Clinic, Cleveland, Ohio, USA.

Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of the Alport syndrome community, as well as offer clarity for future clinical research sponsors, the Alport Syndrome Foundation hosted a workshop to generate consensus recommendations for prospective trials for conventional drugs. Opinions of key stakeholders were carefully considered, including those of the biopharmaceutical industry representatives, academic researchers, clinicians, regulatory agency representatives, and-most critically-patients with Alport syndrome. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.02.029DOI Listing
June 2020
8.563 Impact Factor

Exome Sequencing and Identification of Phenocopies in Patients With Clinically Presumed Hereditary Nephropathies.

Am J Kidney Dis 2020 Apr 28. Epub 2020 Apr 28.

Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. Electronic address:

Rationale & Objective: Hereditary nephropathies are clinically and genetically heterogeneous disorders. For some patients, the clinical phenotype corresponds to a specific hereditary disease but genetic testing reveals that the expected genotype is not present (phenocopy). The aim of this study was to evaluate the spectrum and frequency of phenocopies identified by using exome sequencing in a cohort of patients who were clinically suspected to have hereditary kidney disorders. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2019.12.008DOI Listing
April 2020
5.900 Impact Factor

Femtosecond laser-assisted cataract surgery for bilateral anterior lenticonus.

J Cataract Refract Surg 2020 May;46(5):789-791

From the Department of Ophthalmology, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.

Anterior lenticonus is a characteristic ocular feature of Alport syndrome, leading to progressive vision deterioration. Surgical lens removal may be an option in such cases, and the role of femtosecond laser-assisted cataract surgery (FLACS) has been recently described. Herein, we report the third described case, to our knowledge, of bilateral anterior lenticonus surgically approached through FLACS. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.jcrs.0000000000000186DOI Listing

Thrombosis risk of Alport syndrome patients: evaluation of cardiological, clinical, biochemical, genetic and possible causes of inherited thrombophilia and identification of a novel COL4A3 variant.

Blood Coagul Fibrinolysis 2020 Jun;31(4):264-269

Department of Pediatrics, Duzce University Medical Faculty, Düzce, Turkey.

: To evaluate cases with Alport syndrome for laboratory, radiological, ophthalmological, auditory tests, cardiological and inherited thrombophilia risk. Laboratory findings, abdominal and urinary ultrasonography, ophthalmological and auditory tests and cardiological examination of 21 Alport syndrome suspicious cases were performed. Also, collagen type IV alpha three chain (COL4A3) gene, four chain (COL4A4) gene and five chain (COL4A5) genes were sequenced by next-generation sequencing system. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0000000000000911DOI Listing

The First COL4A5 Exon 41A Glycine Substitution in a Family With Alport Syndrome.

Front Pediatr 2020 9;8:153. Epub 2020 Apr 9.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

X-linked Alport syndrome is caused by mutations in the COL4A5 gene, which encodes the a5(IV) chain. No mutations were detected in COL4A5 exons 41A and 41B. A Chinese family with suspected Alport syndrome was enrolled in the present study to establish a precise diagnosis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2020.00153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160674PMC

Alport Syndrome and Femtosecond Laser-assisted Cataract Surgery.

J Ophthalmic Vis Res 2020 Apr-Jun;15(2):264-269. Epub 2020 Apr 6.

Department of Cataract and Refractive Surgery, Clínica Vistahermosa, Oftalvist Alicante, Alicante, Spain.

We report the surgical management of a patient with bilateral anterior lenticonus due to Alport syndrome using femtosecond laser-assisted cataract surgery (FLACS) and the Optiwave Refractive Analysis (ORA) system. A 38-year-old man with Alport syndrome presented to our department with visual loss due to anterior lenticonus in both eyes. Adjustments during bilateral FLACS were performed with the software's calipers to manually delineate the anterior capsulotomy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.18502/jovr.v15i2.6748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151501PMC

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome.

Kidney Int 2020 Jun 17;97(6):1275-1286. Epub 2020 Jan 17.

Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.

Children with Alport syndrome develop renal failure early in life. Since the safety and efficacy of preemptive nephroprotective therapy are uncertain we conducted a randomized, placebo-controlled, double-blind trial in 14 German sites of pediatric patients with ramipril for three to six years plus six months follow-up to determine these parameters. Pretreated children and those whose parents refused randomization became an open-arm control, which were compared to prospective real-world data from untreated children. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2019.12.015DOI Listing

Alport's Syndrome: A Rare Clinical Presentation with Crescents.

Indian J Nephrol 2020 Mar-Apr;30(2):129-131. Epub 2020 Feb 7.

Department of Nephrology, Aditya Birla Memorial Hospital, Pune, Maharashtra, India.

Alport's syndrome (hereditary nephritis) is a familial disorder, which usually affects young males with clinical presentation of hematuric and glomerular disease. We report a rare case of Alport's syndrome in a 16-year-old male with typical extrarenal manifestations and renal biopsy findings with crescents. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijn.IJN_177_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132844PMC
February 2020

Pericyte abnormalities precede strial capillary basement membrane thickening in Alport mice.

Hear Res 2020 May 18;390:107935. Epub 2020 Mar 18.

Boys Town National Research Hospital, Omaha, NE, USA. Electronic address:

In 129 Sv autosomal Alport mice, the strial capillary basement membranes (SCBMs) progressively thicken between 5 and 9 weeks of age resulting in a hypoxic microenvironment with metabolic stress and induction of pro-inflammatory cytokines and chemokines. These events occur concomitant with a drop in endocochlear potential and a susceptibility to noise-induced hearing loss under conditions that do not permanently affect age/strain-matched littermates. Here we aimed to gain an understanding of events that occur before the onset of SCBM thickening. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heares.2020.107935DOI Listing

How to resolve confusion in the clinical setting for the diagnosis of heterozygous COL4A3 or COL4A4 gene variants? Discussion and suggestions from nephrologists.

Clin Exp Nephrol 2020 Mar 30. Epub 2020 Mar 30.

Nephrology Center, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo, 105-8470, Japan.

Both thin basement membrane nephropathy (TBMN) and autosomal dominant Alport syndrome (ADAS) are types of hereditary nephritis resulting from heterozygous mutations in COL4A3 or COL4A4 genes. Although TBMN is characterized by hematuria and thinning of the glomerular basement membrane (GBM) with excellent renal prognosis, some patients develop end-stage renal disease (ESRD) later in life. In contrast, although AS is characterized by progressive nephropathy with lamellation of the GBM, there are some patients diagnosed with ADAS from a family history of ESRD but who only suffer from hematuria with GBM thinning. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10157-020-01880-1DOI Listing

Multiple Vitelliform Lesions as a Retinal Manifestation of Alport Syndrome.

Case Rep Ophthalmol 2020 Jan-Apr;11(1):79-84. Epub 2020 Feb 12.

Department of Ophthalmology, Oslo University Hospital, Oslo, Norway.

Alport syndrome is associated with various ocular phenotypic features, including several retinal manifestations. The purpose of this case report was to describe a case of multiple vitelliform lesions in Alport syndrome. This particular finding has, to our knowledge, not been reported previously. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1159/000505948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098359PMC
February 2020

Revisiting the complement system in systemic lupus erythematosus.

Expert Rev Clin Immunol 2020 Apr 6;16(4):397-408. Epub 2020 Apr 6.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease, characterized by the production of autoantibodies. Numerous mechanisms contribute to the pathogenesis and autoimmunity in SLE. One of the most important mechanisms is the defective function of the early complement components that are involved in clearing the immune-complexes and apoptotic debris. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1080/1744666X.2020.1745063DOI Listing

FEMTOSECOND LASER ASSSITED CATARACT SURGERY FOR BILATERAL ANTERIOR LENTICONUS.

J Cataract Refract Surg 2020 Mar 20. Epub 2020 Mar 20.

- Department of Ophthalmology, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.

Anterior lenticonus is a characteristic ocular feature of Alport syndrome, leading to progressive vision deterioration. Surgical lens removal may be an option in such cases and the role of femtosecond laser assisted cataract surgery (FLACS) has been recently described. Herein we report the third described case, to our knowledge, of bilateral anterior lenticonus surgically approached through FLACS. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.jcrs.0000000000000186DOI Listing

Initial experience from a renal genetics clinic demonstrates a distinct role in patient management.

Genet Med 2020 Mar 17. Epub 2020 Mar 17.

Departments of Internal Medicine, University of Iowa, Iowa City, IA, USA.

Purpose: A Renal Genetics Clinic (RGC) was established to optimize diagnostic testing, facilitate genetic counseling, and direct clinical management.

Methods: Retrospective review of patients seen over a two-year period in the RGC.

Results: One hundred eleven patients (mean age: 39. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-020-0772-yDOI Listing

Pediatric glomerular hematuria: a clinicopathological study.

Clin Exp Nephrol 2020 Jul 20;24(7):613-621. Epub 2020 Mar 20.

Pediatric Nephrology Unit, Departement of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.

Background: Hematuria is a common problem in pediatric practice and necessitates exhausting studies to detect etiology and establish proper management and counselling.

Subjects And Methods: We reviewed the clinical and pathological findings in 95 children presented between 2013 and 2019 with gross or microscopic hematuria with or without proteinuria in whom non-glomerular causes were excluded. In addition, a reference range for normal glomerular basement membrane thickness (GBMT) is introduced based on the assessment of biopsies of 20 steroid-resistant nephrotic syndrome cases aged 3-15 years, and with minimal change pathology. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10157-020-01872-1DOI Listing

Corneal endothelial cell abnormalities in X-linked Alport syndrome.

Ophthalmic Genet 2020 02 11;41(1):13-19. Epub 2020 Mar 11.

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

: X-linked Alport syndrome results from the effect of  mutations on basement membranes in the kidney, ear and eye. This study investigated individuals with X-linked Alport syndrome for corneal abnormalities.: Six men and four women from 8 families with genetically-diagnosed X-linked Alport syndrome underwent ophthalmological examination including slit lamp examination and corneal endothelial specular microscopy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1080/13816810.2019.1709126DOI Listing
February 2020

Pulmonary manifestations of systemic karyomegaly.

Respir Med Case Rep 2020 26;29:101032. Epub 2020 Feb 26.

Institute of Biomedicine, Department of Laboratory Medicine, Division of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Over 40 years ago, abnormal enlargement of the nucleus of tubular epithelial cells was reported in a rare distinct hereditary chronic interstitial nephritis, karyomegalic interstitial nephritis (KIN). Here, we report the second case of systemic karyomegaly with pulmonary manifestations and present a detailed characterization of the karyomegalic cells in lung parenchyma. A 59-year-old woman who was diagnosed with KIN developed renal failure and eventually received a renal transplant later evaluated for chronic and progressive restrictive lung disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmcr.2020.101032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058920PMC
February 2020

Angiotensin-[1-7] attenuates kidney injury in experimental Alport syndrome.

Sci Rep 2020 Mar 6;10(1):4225. Epub 2020 Mar 6.

Departments of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

Angiotensin-[1-7] (Ang-[1-7]) antagonize the actions of the renin-angiotensin-system via the Mas receptor and thereby exert renoprotective effects. Murine recombinant angiotensin-converting enzyme (ACE)2 was reported to show renoprotective effects in an experimental Alport syndrome model; however, the protective effect of direct administration of Ang-[1-7] is unknown. Here, we used Col4a3 mice as a model of Alport syndrome, which were treated with saline or Ang- [1-7]; saline-treated wild-type mice were used as a control group. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-61250-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060323PMC

Endoplasmic Reticulum Stress Activation in Alport Syndrome Varies Between Genotype and Cell Type.

Front Genet 2020 10;11:36. Epub 2020 Feb 10.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Alport syndrome is a hereditary progressive chronic kidney disease caused by mutations in type IV collagen genes . X-linked Alport syndrome (XLAS) is caused by mutations in the gene and is the most common form of Alport syndrome. A strong correlation between the type of mutation and the age developing end-stage renal disease in male patients has been found. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025644PMC
February 2020

Karyomegalic interstitial nephritis with a novel FAN1 gene mutation and concurrent ALECT2 amyloidosis.

BMC Nephrol 2020 Feb 28;21(1):74. Epub 2020 Feb 28.

UCL Department of Renal Medicine, Centre for Experimental Nephrology, Royal Free Hospital, NW3 2PF, London, UK.

Background: Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic kidney disease. It typically causes progressive renal impairment with haemoproteinuria requiring renal replacement therapy before 50 years of age. It has been associated with mutations in the Fanconi anaemia-associated nuclease 1 (FAN1) gene and has an autosomal recessive pattern of inheritance. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-020-01733-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049196PMC
February 2020

Epidemiology of 10-year paediatric renal biopsies in the region of southern Croatia.

BMC Nephrol 2020 Feb 26;21(1):65. Epub 2020 Feb 26.

Department of Pediatrics, University Hospital Centre Split, 21000, Split, Croatia.

Background: Information about renal diseases in children is available from national registries of renal biopsies. Aim of the study was to compare the clinical presentation of glomerular diseases and tubulointerstitial space diseases with pathohistological diagnosis of indicated renal biopsies from pediatric population in the Croatian region of Dalmatia.

Methods: Out of 231 pediatric patients with suspected glomerular and tubulointerstitial diseases, 54 underwent ultrasound-guided renal biopsy at University Hospital of Split. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-020-01727-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045640PMC
February 2020

CG200745, a Novel HDAC Inhibitor, Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome.

Int J Mol Sci 2020 Feb 21;21(4). Epub 2020 Feb 21.

Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea.

Histone deacetylases have been a target of therapy for organ fibrosis. Here, we report the protective effect of CG200745 (CG), a novel histone deacetylase inhibitor, on tubulointerstitial fibrosis in mice, a murine model of Alport syndrome. Morphological analyses revealed CG treatment markedly alleviated kidney fibrosis in mice at the age of 7 weeks. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21041473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073208PMC
February 2020

Adverse effects of Alport syndrome-related Gly missense mutations on collagen type IV: Insights from molecular simulations and experiments.

Biomaterials 2020 May 12;240:119857. Epub 2020 Feb 12.

Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA. Electronic address:

Patients with Alport syndrome (AS) exhibit blood and elevated protein levels in their urine, inflamed kidneys, and many other abnormalities. AS is attributed to mutations in type IV collagen genes, particularly glycine missense mutations in the collagenous domain of COL4A5 that disrupt common structural motifs in collagen from the repeat (Gly-Xaa-Yaa) amino acid sequence. To characterize and elucidate the molecular mechanisms underlying how AS-related mutations perturb the structure and function of type IV collagen, experimental studies and molecular simulations were integrated to investigate the structure, stability, protease sensitivity, and integrin binding affinity of collagen-like proteins containing amino acid sequences from the α5(IV) chain and AS-related Gly missense mutations. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2020.119857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071996PMC
May 2020
8.557 Impact Factor

SGLT2 inhibitors - a potential treatment for Alport syndrome.

Clin Sci (Lond) 2020 Feb;134(4):379-388

Renal Services, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, U.K.

Alport syndrome is a rare genetic disease that results in disordered basement membrane type IV collagen resulting in occular and auditory defects as well of progressive kidney disease. Although no 'cure' currently exists, therapeutic blockade of the renin-angiotensin-aldosterone system can slow the progression to end-stage kidney disease (ESKD). Clinical trials for treatments in preventing chronic kidney disease have largely been negative over the last two decades until recent trials have shown positive cardiovascular and renal outcomes of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with diabetes mellitus. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1042/CS20191276DOI Listing
February 2020

Genetic Testing in Pediatric Kidney Disease.

Indian J Pediatr 2020 Feb 13. Epub 2020 Feb 13.

Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India.

The advent of next gene sequencing technology has led to the publication of a profusion of papers on monogenic contributions to pediatric kidney disorders. It started with the discovery of mutations in the podocin gene in steroid resistant nephrotic syndrome (SRNS). It is realized now that genetic disorders contribute to about 30% of chronic renal diseases in children, and significantly to many other kidney disorders. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12098-020-03198-yDOI Listing
February 2020

Anti-Factor B Antibodies and Acute Postinfectious GN in Children.

J Am Soc Nephrol 2020 Apr 7;31(4):829-840. Epub 2020 Feb 7.

Inflammation, Complement and Cancer Team, Cordeliers Research Center, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) S1138, Paris, France;

Background: The pathophysiology of the leading cause of pediatric acute nephritis, acute postinfectious GN, including mechanisms of the pathognomonic transient complement activation, remains uncertain. It shares clinicopathologic features with C3 glomerulopathy, a complement-mediated glomerulopathy that, unlike acute postinfectious GN, has a poor prognosis.

Methods: This retrospective study investigated mechanisms of complement activation in 34 children with acute postinfectious GN and low C3 level at onset. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2019080851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191928PMC

Phenotypic Spectrum of the Foveal Configuration and Foveal Avascular Zone in Patients With Alport Syndrome.

Invest Ophthalmol Vis Sci 2020 02;61(2)

,.

Purpose: To investigate characteristics of the foveal pit and the foveal avascular zone (FAZ) in patients with Alport syndrome (AS), a rare monogenetic disease due to mutations in genes encoding for collagen type IV.

Methods: Twenty-eight eyes of nine patients with AS, and five autosomal-recessive carriers and 15 eyes from 15 age-similar healthy control subjects were examined using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Foveal configuration and FAZ measures including the FAZ area, circularity, and vessel density in the central 1° and 3° were correlated. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.61.2.5DOI Listing
February 2020

A Novel Splicing Mutation Causes Skipping of Exon 14 in a Chinese Family with Alport Syndrome.

Kidney Dis (Basel) 2020 Jan 22;6(1):43-49. Epub 2019 Oct 22.

National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Background: Alport syndrome (AS) is an inherited progressive renal disease caused by mutations in , and . Although mutation screening in the genes responsible for AS is typically performed, only a small proportion of patients receive genetic testing in China, and the functional consequences of multiple splicing variants in AS patients have not been investigated.

Methods: A family with X-linked AS was diagnosed based on family history and pathological findings from a kidney biopsy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1159/000502798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995980PMC
January 2020

X-linked Alport syndrome with "empty capsule sign".

Kidney Int 2020 Feb;97(2):426

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA. Electronic address:

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2019.08.025DOI Listing
February 2020

A novel mutation in a Chinese family with autosomal recessive Alport syndrome: a case report.

Int J Clin Exp Pathol 2019 1;12(9):3565-3569. Epub 2019 Sep 1.

Department of Pathology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine Shenzhen 518033, Guangdong, China.

Alport syndrome (AS) is a familial hereditary nephropathy which is characterized by molecular abnormalities in Collagen IV a345. As more gene mutations are discovered, it has been reported that autosomal recessive disease accounts for a smaller proportion (about 4%) of AS patients than previously recognized. We report here a novel mutation in in a Chinese family with autosomal recessive AS. Read More

View Article

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949818PMC
September 2019

Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome.

Nephrology (Carlton) 2020 Jun 29;25(6):497-501. Epub 2020 Jan 29.

Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/nep.13693DOI Listing

[Analysis of Alport syndrome induced by type IV collagen alpha 5 gene mutation in two families].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2019 Jun;48(4):384-389

Department of Nephrology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.

Objective: To investigate genetic characteristics of Alport syndrome.

Methods: High-throughput sequencing-based whole exome sequencing was performed in two patients with recurrent unexplained abnormal urinalysis. The pathogenicity of the genetic variations, type of Mendelian genetics, and clinical phenotypes were analysed, and the disease-cause mutations were confirmed in the family members using Sanger sequencing. Read More

View Article

Download full-text PDF

Source

Detection of Cryptic Mosaicism in X-linked Alport Syndrome Prompts to Reevaluate Living-donor Kidney Transplantation.

Transplantation 2019 Dec 31. Epub 2019 Dec 31.

Medical Genetics, University of Siena, Siena, Italy.

Background: Alport syndrome (AS) is a hereditary nephropathy caused by mutations in collagen IV genes and characterized by ultrastructural lesions of the glomerular basement membrane. Some patients have a negative family history with apparently de novo mutations. Although somatic mosaicism has been postulated, as cryptic mosaicism cannot be detected from mutational screening on peripheral blood samples, cases in kidney-confined mosaic form have been missed. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003104DOI Listing
December 2019
3.828 Impact Factor

Modification of an aggressive model of Alport Syndrome reveals early differences in disease pathogenesis due to genetic background.

Sci Rep 2019 12 31;9(1):20398. Epub 2019 Dec 31.

Renal and Vascular Inflammation Section, Department of Medicine, Imperial College, London, W12 0N, UK.

The link between mutations in collagen genes and the development of Alport Syndrome has been clearly established and a number of animal models, including knock-out mouse lines, have been developed that mirror disease observed in patients. However, it is clear from both patients and animal models that the progression of disease can vary greatly and can be modified genetically. We have identified a point mutation in Col4a4 in mice where disease is modified by strain background, providing further evidence of the genetic modification of disease symptoms. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-56837-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938516PMC
December 2019

An Exome Sequencing Study of 10 Families with IgA Nephropathy.

Nephron 2020 19;144(2):72-83. Epub 2019 Dec 19.

Department of Nephrology and Transplantation, Beaumont Hospital, Dublin, Ireland.

Background: Immunoglobulin A nephropathy (IgAN) is a heterogeneous disorder with a strong genetic component. The advent of whole exome sequencing (WES) has accelerated the discovery of genetic risk factors underlying familial disorders.

Objectives: We set out to test whether damaging variants in known kidney disease genes explain a proportion of IgAN cases recruited in Ireland. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1159/000503564DOI Listing
December 2019

The Hypomorphic Variant p.(Gly624Asp) in as a Possible Cause for an Unexpected Severe Phenotype in a Family With X-Linked Alport Syndrome.

Front Pediatr 2019 26;7:485. Epub 2019 Nov 26.

Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.

Alport syndrome (AS) is a progressive kidney disorder leading to end stage renal disease (ESRD). Extrarenal symptoms like hearing loss and ocular changes can be observed. Approximately 85% of the patients carry pathogenic variants in (X-linked inheritance). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2019.00485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887795PMC
November 2019

IgA nephropathy suspected to be combined with Fabry disease or Alport syndrome: a case report.

J Int Med Res 2019 Dec 16:300060519891290. Epub 2019 Dec 16.

North Sichuan Medical College, Nanchong, Sichuan, China.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300060519891290DOI Listing
December 2019

Utility of Genomic Testing after Renal Biopsy.

Am J Nephrol 2020 10;51(1):43-53. Epub 2019 Dec 10.

Department of Nephrology and Transplantation, Beaumont Hospital, Dublin, Ireland.

Background: Renal biopsy is the mainstay of renal pathological diagnosis. Despite sophisticated diagnostic techniques, it is not always possible to make a precise pathological diagnosis. Our aim was to identify a genetic cause of disease in patients who had undergone renal biopsy and determine if genetic testing altered diagnosis or treatment. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1159/000504869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957728PMC
December 2019
5 Reads

Multiple Coronary Artery Aneurysms in Alport Syndrome.

J Invasive Cardiol 2019 Dec;31(12):E392-E393

Department of Cardiology and Intensive Care, "St. Josef" Hospital, Braunau, Austria.

Alport syndrome (AS) is a genetic disorder characterized by abnormal alpha chains of type IV collagen in multiple organs including the kidney, cochlea, cornea, lens, and retina. Aortic disease including dissection and aneurysm has been described with AS. We report the first case of multiple coronary aneurysms as a manifestation of AS. Read More

View Article

Download full-text PDF

Source
December 2019
4 Reads

Soluble Urokinase Receptor Levels in Secondary Focal Segmental Glomerulosclerosis.

Kidney Dis (Basel) 2019 Oct 27;5(4):239-246. Epub 2019 May 27.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Background: Soluble urokinase receptor (suPAR) has been reported to be a possible permeability factor causing primary focal segmental glomerulosclerosis (FSGS) in recent years. We investigated the plasma and urinary suPAR levels in patients with 3 common types of secondary FSGS: Alport's syndrome (Alport-FSGS), obesity-related FSGS, and diabetic nephropathy.

Methods: Fifty-two secondary FSGS patients diagnosed by kidney biopsy, including 8 with Alport-FSGS, 20 with obesity-related FSGS, and 24 with diabetic nephropathy, were enrolled in the study in the period from January 2008 to June 2014 at the Renal Division, Peking University First Hospital. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1159/000497353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873037PMC
October 2019

Alport-leiomyomatosis syndrome requiring subtotal esophagectomy for refractory gastroesophageal reflux disease after childhood partial esophagogastrectomy: a case report.

Gen Thorac Cardiovasc Surg 2020 Feb 22;68(2):199-203. Epub 2019 Nov 22.

Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Japan.

Alport-leiomyomatosis syndrome is an extremely rare condition occurring at a young age in which Alport syndrome coexists with diffuse leiomyomatosis of the digestive tract (primarily the esophagus). Most patients with diffuse esophageal leiomyomatosis require esophagectomy of variable extents. A 20-year-old man with Alport-leiomyomatosis syndrome was diagnosed with dysphasia and hematuria in childhood. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11748-019-01255-8DOI Listing
February 2020