Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Yanglin, Li, Wei, Tian, Lulu, Fu, Shuai, Min, Yonglong, Liu, Jia, Xiong, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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
_version_ 1784685789955751936
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
work_keys_str_mv AT huyanglin casereportidentificationofanovelheterozygousmissensemutationincol4a3genecausingvariablephenotypesinanautosomaldominantalportsyndromefamily
AT liwei casereportidentificationofanovelheterozygousmissensemutationincol4a3genecausingvariablephenotypesinanautosomaldominantalportsyndromefamily
AT tianlulu casereportidentificationofanovelheterozygousmissensemutationincol4a3genecausingvariablephenotypesinanautosomaldominantalportsyndromefamily
AT fushuai casereportidentificationofanovelheterozygousmissensemutationincol4a3genecausingvariablephenotypesinanautosomaldominantalportsyndromefamily
AT minyonglong casereportidentificationofanovelheterozygousmissensemutationincol4a3genecausingvariablephenotypesinanautosomaldominantalportsyndromefamily
AT liujia casereportidentificationofanovelheterozygousmissensemutationincol4a3genecausingvariablephenotypesinanautosomaldominantalportsyndromefamily
AT xiongfei casereportidentificationofanovelheterozygousmissensemutationincol4a3genecausingvariablephenotypesinanautosomaldominantalportsyndromefamily