scholarly journals Identification of a novel collagen type IV alpha-4 (COL4A4) mutation in a Chinese family with autosomal dominant Alport syndrome using exome sequencing

2016 ◽  
Vol 144 (2) ◽  
pp. 200 ◽  
Author(s):  
Hao Deng ◽  
Sheng Deng ◽  
Hongbo Xu ◽  
Jinzhong Yuan ◽  
Jingjing Xiao ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Collagen Type ◽  
Chinese Family ◽  
Collagen Type Iv ◽  
Type Iv

Renal distribution of collagen type IV α chains in autosomal-dominant Alport syndrome

1998 ◽  
Vol 2 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Ichiro Naito ◽  
Shinsuke Nomura ◽  
Shinichiro Kawai ◽  
Satoko Inoue ◽  
J. Ashley Jefferson ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Collagen Type ◽  
Collagen Type Iv ◽  
Type Iv

scholarly journals A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

2021 ◽  
Author(s):  
Qing Li ◽  
Chengfeng Wang ◽  
Wei Li ◽  
Zaiqiang Zhang ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Skin Biopsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Collagen Type Iv ◽  
Lacunar Infarcts ◽  
Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

scholarly journals Regulation of collagen type IV genes is organ-specific: Evidence from a canine model of Alport syndrome

2005 ◽  
Vol 68 (5) ◽  
pp. 2121-2130 ◽  
Author(s):  
Keqin Zheng ◽  
Julie Perry ◽  
Scott J. Harvey ◽  
Yoshikazu Sado ◽  
Yoshifumi Ninomiya ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Collagen Type ◽  
Canine Model ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Organ Specific

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

Biomaterials ◽  
2020 ◽  
Vol 240 ◽  
pp. 119857 ◽  
Author(s):  
Jingjie Yeo ◽  
Yimin Qiu ◽  
Gang Seob Jung ◽  
Yong-Wei Zhang ◽  
Markus J. Buehler ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Alport Syndrome ◽  
Collagen Type ◽  
Molecular Simulations ◽  
Collagen Type Iv ◽  
Missense Mutations ◽  
Type Iv

scholarly journals Endothelial cell-specific collagen type IV-α3expression does not rescue Alport syndrome inCol4a3−/−mice

2019 ◽  
Vol 316 (5) ◽  
pp. F830-F837 ◽  
Author(s):  
Steven D. Funk ◽  
Raymond H. Bayer ◽  
Jeffrey H. Miner
Keyword(s):  
Gene Therapy ◽  
Endothelial Cell ◽  
Alport Syndrome ◽  
Collagen Type ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Collagen Type Iv ◽  
Gene Repair ◽  
Type Iv ◽  
Filtration Barrier

The glomerular basement membrane (GBM) is a critical component of the kidney’s blood filtration barrier. Alport syndrome, a hereditary disease leading to kidney failure, is caused by the loss or dysfunction of the GBM’s major collagen type IV (COL4) isoform α3α4α5. The constituent COL4 α-chains assemble into heterotrimers in the endoplasmic reticulum before secretion into the extracellular space. If any one of the α3-, α4-, or α5-chains is lost due to mutation of one of the genes, then the entire heterotrimer is lost. Patients with Alport syndrome typically have mutations in the X-linked COL4A5 gene or uncommonly have the autosomal recessive form of the disease due to COL4A3 or COL4A4 mutations. Treatment for Alport syndrome is currently limited to angiotensin-converting enzyme inhibition or angiotensin receptor blockers. Experimental approaches in Alport mice have demonstrated that induced expression of COL4A3, either widely or specifically in podocytes of Col4a3−/−mice, can abrogate disease progression even after establishment of the abnormal GBM. While targeting podocytes in vivo for gene therapy is a significant challenge, the more accessible glomerular endothelium could be amenable for mutant gene repair. In the present study, we expressed COL4A3 in Col4a3−/−Alport mice using an endothelial cell-specific inducible transgenic system, but collagen-α3α4α5(IV) was not detected in the GBM or elsewhere, and the Alport phenotype was not rescued. Our results suggest that endothelial cells do not express the Col4a3/a4/a5 genes and should not be viewed as a target for gene therapy.

scholarly journals Absence of the α6(IV) Chain of Collagen Type IV in Alport Syndrome Is Related to a Failure at the Protein Assembly Level and Does Not Result in Diffuse Leiomyomatosis

1999 ◽  
Vol 154 (6) ◽  
pp. 1883-1891 ◽  
Author(s):  
Keqin Zheng ◽  
Scott Harvey ◽  
Yoshikazu Sado ◽  
Ichiro Naito ◽  
Yoshifumi Ninomiya ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Collagen Type ◽  
Protein Assembly ◽  
Collagen Type Iv ◽  
Type Iv

scholarly journals A NovelCOL4A5Mutation Identified in a Chinese Han Family Using Exome Sequencing

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Xiaofei Xiu ◽  
Jinzhong Yuan ◽  
Xiong Deng ◽  
Jingjing Xiao ◽  
Hongbo Xu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Exome Sequencing ◽  
Collagen Type ◽  
Corneal Dystrophy ◽  
Sensorineural Hearing ◽  
Monogenic Disease ◽  
Collagen Type Iv ◽  
Chinese Han ◽  
Type Iv

Alport syndrome (AS) is a monogenic disease of the basement membrane (BM), resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and ocular anomalies. It is caused by mutations in the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alpha-4 gene (COL4A4), and the collagen type IV alpha-5 gene (COL4A5), which encodes type IV collagenα3,α4, andα5 chains, respectively. To explore the disease-related gene in a four-generation Chinese Han pedigree of AS, exome sequencing was conducted on the proband, and a novel deletion mutation c.499delC (p.Pro167Glnfs*36) in theCOL4A5gene was identified. This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family. Neither sensorineural hearing loss nor typicalCOL4A5-related ocular abnormalities (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy) were present in patients of this family. The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD). Our discovery broadens the mutation spectrum in theCOL4A5gene associated with AS, which may also shed new light on genetic counseling for AS.

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