Effect of heterozygous pathogenic COL4A3 or COL4A4 variants on patients with X ‐linked Alport syndrome

In this study, three children showed coexisting pathogenic variants inCOL4A5 andCOL4A3. Two children showed pathogenic variants inCOL4A5 andCOL4A4. One child had pathogenic variants in the threeCOL4A3 ‐5 genes, in which the pathogenic variant inCOL4A5 was de novo and the pathogenic variants inCOL4A4 andCOL4A3 were inherited independently (in trans). The site and type of mutations inCOL4A5were similar between the two groups. It was revealed that males in group 1 presented more severe proteinuria than males in group 2 (p  
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research

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Alport syndrome (AS) is a hereditary nephropathy characterized by glomerular basement membrane lesions. AS shows a relatively rare entity with autosomal dominant gene mutation (accounts for less than 5 percent of AS cases) and is widely believed to be a consequence of heterozygous variants in the COL4A3 and COL4A4 genes. Until now, there have been no reports of homozygous variants in genes in AS patients, and it is scarce to detect both homozygous and heterozygous variants in a single Alport syndrome pedigree. We performed genetic analysis by exome sequencing (exome-seq) in a Chinese family with AS and found four individua...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
We report a 30-year-old male who presented with proteinuria and elevated serum creatinine and for whom the initial pathologic diagnosis supported Alport syndrome. Diagnoses: A diagnosis of Fabry disease with immunoglobulin A nephropathy (IgAN) was finally made after further examination. Interventions: After the initial diagnosis the patient was treated with herbal medications and mecobalamin. Outcomes: The patient was discharged 1 week later. He was maintained on these treatments and received regular follow-up in our hospital. Lessons subsections as per style: FD coexisting with IgAN is rare and may have nons...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Conclusion: We identified novel mutations in Koreans with an X-linked AS mutation in the COL4A5 gene and an individual phenotype. This is the first report of AS patients with a novel missense mutation and copy number variation.
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
In this study, three children showed coexisting pathogenic variants in COL4A5 and COL4A3. Two children showed pathogenic variants in COL4A5 and COL4A4. One child had pathogenic variants in the three COL4A3-5 genes, in which the pathogenic variant in COL4A5 was de novo and the pathogenic variants in COL4A4 and COL4A3 were inherited independently (in trans). The site and type of mutations in COL4A5 were similar between the two groups. It was revealed that males in group 1 presented more severe proteinuria than males in group 2 (p 
Source: Molecular Medicine - Category: Molecular Biology Authors: Tags: Mol Genet Genomic Med Source Type: research
ConclusionCharacteristic pathological glomerular findings and GBM alterations occurred from a young age but were not associated directly with renal impairment in biopsy-proven TBMN.
Source: Clinical and Experimental Nephrology - Category: Urology & Nephrology Source Type: research
We describe a Caucasian family with concomitantCOL4A3 andCOL4A5 mutations, consisting of a novel c.4484A#x3e;GCOL4A3 (p.Gln1495Arg) mutation and a previously reported c.1871G#x3e;ACOL4A5 (p.Gly624Asp) mutation. Our segregation analysis raises the possibility that Alport syndrome resembles also digenic inheritance byCOL4A3/COL4A5.Nephron
Source: Nephron - Category: Urology & Nephrology Source Type: research
AbstractWe herein report 2 Japanese patients with X-linked Alport syndrome (XLAS), with a novel variant inCOL4A5. 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. When her mother (patient 2) was 40 years of age (3 years after patient 1 underwent a renal biopsy), patient 2 was found to have asymptomatic hematuria, proteinuria, and an increased serum creatinine level, w ithout deafness and ocular abnormalitie...
Source: CEN Case Reports - Category: Urology & Nephrology Source Type: research
AbstractAlport syndrome is a hereditary glomerular basement membrane disease caused by mutations in theCOL4A3/4/5 genes encoding the type IV collagen alpha 3 –5 chains. Most cases of Alport syndrome are inherited as X-linked dominant, and some as autosomal recessive or autosomal dominant. The primary manifestations are hematuria, proteinuria, and progressive renal failure, whereas some patients present with sensorineural hearing loss and ocular abnorma lities. Renin–angiotensin–aldosterone system blockade is proven to delay the onset of renal failure by reducing proteinuria. Renal transplantation is a cur...
Source: Pediatric Nephrology - Category: Urology & Nephrology Source Type: research
We report a unique case of a 9-year-old boy who was biopsied for hematur ia and proteinuria, diagnosed as IgA nephropathy, with normal GBM appearance and thickness. Due to a family history of hematuria and chronic kidney disease, he subsequently underwent genetic evaluation and a mutation of α3 type IV collagen (COL4A3) was detected.
Source: Human Pathology - Category: Pathology Authors: Source Type: research
Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β2 (LAMB2), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin pol...
Source: Journal of the American Society of Nephrology : JASN - Category: Urology & Nephrology Authors: Tags: Basic Research Source Type: research
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