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Case Report: Identification of a Novel Heterozygous Missense Mutation in COL4A3 Gene Causing Variable Phenotypes in an Autosomal-Dominant Alport Syndrome Family
Alport syndrome (AS) is a genetic kidney disease of basement membrane collagen disorder accounting for approximately 2% of ESRD patients. Next-generation and whole-exome sequencing methods are increasingly frequently used as an efficient tool not only for the diagnosis of AS but also for the establi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001967/ https://www.ncbi.nlm.nih.gov/pubmed/35422838 http://dx.doi.org/10.3389/fgene.2022.839212 |
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author | Hu, Yanglin Li, Wei Tian, Lulu Fu, Shuai Min, Yonglong Liu, Jia Xiong, Fei |
author_facet | Hu, Yanglin Li, Wei Tian, Lulu Fu, Shuai Min, Yonglong Liu, Jia Xiong, Fei |
author_sort | Hu, Yanglin |
collection | PubMed |
description | Alport syndrome (AS) is a genetic kidney disease of basement membrane collagen disorder accounting for approximately 2% of ESRD patients. Next-generation and whole-exome sequencing methods are increasingly frequently used as an efficient tool not only for the diagnosis of AS but also for the establishment of genotype–phenotype correlation. We herein report the identification of a novel heterozygous missense mutation in COL4A3 gene (c.G3566A: p.G1189E) causing variable phenotypes in an ADAS Family based on the combination of clinical, histologic, pedigree, and genetic sequencing information. The proband is a 48-year-old Chinese woman suffering from persistent subnephrotic proteinuria and intermittent hematuria without renal function impairment over a 10-year time-span. Renal biopsy showed diffuse thin basement membrane and focal interstitial foam cell infiltration. The proband’s mother progressed to end-stage renal failure and the proband’s sister presented with subnephrotic proteinuria and intermittent hematuria as well. AS was highly suspected and confirmed by exome sequencing which revealed a novel heterozygous missense mutation in COL4A3 gene (c.G3566A: p.G1189E) in all the affected family members, although their current medical conditions vary significantly. Our present finding emphasizes the significance of next-generation sequencing technology for genetic screening which gives us an accurate clinical diagnosis of ADAS patients. The identification of c.G3566A as a new ADAS-related mutation contributes to both genetic diagnosis of ADAS and further functional study of COL4A3. The variable phenotypes from the same genotype of our case also provide more information to genotype–phenotype correlation study. |
format | Online Article Text |
id | pubmed-9001967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90019672022-04-13 Case Report: Identification of a Novel Heterozygous Missense Mutation in COL4A3 Gene Causing Variable Phenotypes in an Autosomal-Dominant Alport Syndrome Family Hu, Yanglin Li, Wei Tian, Lulu Fu, Shuai Min, Yonglong Liu, Jia Xiong, Fei Front Genet Genetics Alport syndrome (AS) is a genetic kidney disease of basement membrane collagen disorder accounting for approximately 2% of ESRD patients. Next-generation and whole-exome sequencing methods are increasingly frequently used as an efficient tool not only for the diagnosis of AS but also for the establishment of genotype–phenotype correlation. We herein report the identification of a novel heterozygous missense mutation in COL4A3 gene (c.G3566A: p.G1189E) causing variable phenotypes in an ADAS Family based on the combination of clinical, histologic, pedigree, and genetic sequencing information. The proband is a 48-year-old Chinese woman suffering from persistent subnephrotic proteinuria and intermittent hematuria without renal function impairment over a 10-year time-span. Renal biopsy showed diffuse thin basement membrane and focal interstitial foam cell infiltration. The proband’s mother progressed to end-stage renal failure and the proband’s sister presented with subnephrotic proteinuria and intermittent hematuria as well. AS was highly suspected and confirmed by exome sequencing which revealed a novel heterozygous missense mutation in COL4A3 gene (c.G3566A: p.G1189E) in all the affected family members, although their current medical conditions vary significantly. Our present finding emphasizes the significance of next-generation sequencing technology for genetic screening which gives us an accurate clinical diagnosis of ADAS patients. The identification of c.G3566A as a new ADAS-related mutation contributes to both genetic diagnosis of ADAS and further functional study of COL4A3. The variable phenotypes from the same genotype of our case also provide more information to genotype–phenotype correlation study. Frontiers Media S.A. 2022-03-29 /pmc/articles/PMC9001967/ /pubmed/35422838 http://dx.doi.org/10.3389/fgene.2022.839212 Text en Copyright © 2022 Hu, Li, Tian, Fu, Min, Liu and Xiong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Hu, Yanglin Li, Wei Tian, Lulu Fu, Shuai Min, Yonglong Liu, Jia Xiong, Fei Case Report: Identification of a Novel Heterozygous Missense Mutation in COL4A3 Gene Causing Variable Phenotypes in an Autosomal-Dominant Alport Syndrome Family |
title | Case Report: Identification of a Novel Heterozygous Missense Mutation in COL4A3 Gene Causing Variable Phenotypes in an Autosomal-Dominant Alport Syndrome Family |
title_full | Case Report: Identification of a Novel Heterozygous Missense Mutation in COL4A3 Gene Causing Variable Phenotypes in an Autosomal-Dominant Alport Syndrome Family |
title_fullStr | Case Report: Identification of a Novel Heterozygous Missense Mutation in COL4A3 Gene Causing Variable Phenotypes in an Autosomal-Dominant Alport Syndrome Family |
title_full_unstemmed | Case Report: Identification of a Novel Heterozygous Missense Mutation in COL4A3 Gene Causing Variable Phenotypes in an Autosomal-Dominant Alport Syndrome Family |
title_short | Case Report: Identification of a Novel Heterozygous Missense Mutation in COL4A3 Gene Causing Variable Phenotypes in an Autosomal-Dominant Alport Syndrome Family |
title_sort | case report: identification of a novel heterozygous missense mutation in col4a3 gene causing variable phenotypes in an autosomal-dominant alport syndrome family |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001967/ https://www.ncbi.nlm.nih.gov/pubmed/35422838 http://dx.doi.org/10.3389/fgene.2022.839212 |
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