Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome

Abstract Nephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management. Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. Here, we used the whole-exome sequencing (WES)...

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Autores principales:	Mohd Fareed, Vikas Makkar, Ravi Angral, Mohammad Afzal, Gurdarshan Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ca61a8b319449509144bd58c28215ad
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spelling	oai:doaj.org-article:4ca61a8b319449509144bd58c28215ad2021-12-02T16:07:03ZWhole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome10.1038/s41598-021-92023-32045-2322https://doaj.org/article/4ca61a8b319449509144bd58c28215ad2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92023-3https://doaj.org/toc/2045-2322Abstract Nephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management. Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. Here, we used the whole-exome sequencing (WES) technology to decipher the genetic cause of nephrotic syndrome (CKD stage-V) in a large affected consanguineous family. Our study exposed a novel missense homozygous mutation NC_000019.9:g.41209497C > T; NM_024876.4:c.748G > A; NP_079152.3:p.(Asp250Asn) in the 9th exon of the COQ8B gene, co-segregated well with the disease phenotype. Our study provides the first insight into this homozygous condition, which has not been previously reported in 1000Genome, ClinVar, ExAC, and genomAD databases. In addition to the pathogenic COQ8B variant, the WES data also revealed some novel and recurrent mutations in the GLA, NUP107, COQ2, COQ6, COQ7 and COQ9 genes. The novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions: SCV001451361.1, SCV001451725.1 and SCV001451724.1. Based on the patient's clinical history and genomic data with in silico validation, we conclude that pathogenic mutation in the COQ8B gene was causing kidney failure in an autosomal recessive manner. We recommend WES technology for genetic testing in such a consanguineous family to not only prevent the future generation, but early detection can help in disease management and therapeutic interventions.Mohd FareedVikas MakkarRavi AngralMohammad AfzalGurdarshan SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohd Fareed Vikas Makkar Ravi Angral Mohammad Afzal Gurdarshan Singh Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome
description	Abstract Nephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management. Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. Here, we used the whole-exome sequencing (WES) technology to decipher the genetic cause of nephrotic syndrome (CKD stage-V) in a large affected consanguineous family. Our study exposed a novel missense homozygous mutation NC_000019.9:g.41209497C > T; NM_024876.4:c.748G > A; NP_079152.3:p.(Asp250Asn) in the 9th exon of the COQ8B gene, co-segregated well with the disease phenotype. Our study provides the first insight into this homozygous condition, which has not been previously reported in 1000Genome, ClinVar, ExAC, and genomAD databases. In addition to the pathogenic COQ8B variant, the WES data also revealed some novel and recurrent mutations in the GLA, NUP107, COQ2, COQ6, COQ7 and COQ9 genes. The novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions: SCV001451361.1, SCV001451725.1 and SCV001451724.1. Based on the patient's clinical history and genomic data with in silico validation, we conclude that pathogenic mutation in the COQ8B gene was causing kidney failure in an autosomal recessive manner. We recommend WES technology for genetic testing in such a consanguineous family to not only prevent the future generation, but early detection can help in disease management and therapeutic interventions.
format	article
author	Mohd Fareed Vikas Makkar Ravi Angral Mohammad Afzal Gurdarshan Singh
author_facet	Mohd Fareed Vikas Makkar Ravi Angral Mohammad Afzal Gurdarshan Singh
author_sort	Mohd Fareed
title	Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome
title_short	Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome
title_full	Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome
title_fullStr	Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome
title_full_unstemmed	Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome
title_sort	whole-exome sequencing reveals a novel homozygous mutation in the coq8b gene associated with nephrotic syndrome
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4ca61a8b319449509144bd58c28215ad
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Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome

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