Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report

Pelizaeus-Merzbacher-Like Disease 1 is a genetic disorder affecting the central nervous system with an autosomal recessive inheritance pattern. It is a rare genetic disorder that affects the central nervous system. In this report, we demonstrated the clinical and paraclinical features of an Iranian...

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Autores principales:	Sepehr Javadikooshesh, Hooshang Zaimkohan, Parisa Pourghorban, Fatemeh Bahramim, Nader Ebadi
Formato:	article
Lenguaje:	EN
Publicado:	Shiraz University of Medical Sciences 2021
Materias:	leukodystrophy, hypomyelinating, 2 mutation whole exome sequencing central nervous system diseases Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3ef2fd1a7b6e41edb1341fb032085209
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spelling	oai:doaj.org-article:3ef2fd1a7b6e41edb1341fb0320852092021-11-09T06:23:38ZPelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report0253-07161735-368810.30476/ijms.2021.87126.1736https://doaj.org/article/3ef2fd1a7b6e41edb1341fb0320852092021-11-01T00:00:00Zhttps://ijms.sums.ac.ir/article_47692_e9c83525db75c165654e3fe8170124f3.pdfhttps://doaj.org/toc/0253-0716https://doaj.org/toc/1735-3688Pelizaeus-Merzbacher-Like Disease 1 is a genetic disorder affecting the central nervous system with an autosomal recessive inheritance pattern. It is a rare genetic disorder that affects the central nervous system. In this report, we demonstrated the clinical and paraclinical features of an Iranian consanguine pedigree with suspected hypomyelinating leukodystrophy, without any defined diagnosis. The proband, a 15-month-old girl, visited the Razi pathobiology and medical genetic laboratory of Karaj, where the study was conducted in 2020. Following whole-exome sequencing analysis of the proband and segregation analysis, a novel pathogenic mutation was discovered. GJC2 (NM_020435.4):c.1096dupG was found to be homozygous in the proband and heterozygous in both parents. This mutation was in the coding region of the protein, which results in D366Gfs*126 (p.Asp366GlyfsTer126). The site of mutation was at the 3’ region of the connexin superfamily domain. The frameshift results in a different peptide sequence of the C-terminal and extended protein. Our findings led to the diagnosis of the proband’s disease as Pelizaeus-Merzbacher-Like Disease 1 and led to the end of the diagnostic odyssey. We provided effective genetic counseling through the identification of a novel pathogenic mutation in gap junction protein C2 in this family and suggested preimplantation genetic diagnosis for the next pregnancy. Furthermore, our findings confirmed the association of GJC2 mutations with PMLD1. This discovery added to the repertoire of genetic mutations of Pelizaeus-Merzbacher-Like Disease 1. This knowledge could be applied for expanded carrier screening of other families, especially for Iranian consanguine marriages.Sepehr JavadikoosheshHooshang ZaimkohanParisa PourghorbanFatemeh BahramimNader EbadiShiraz University of Medical Sciencesarticleleukodystrophy, hypomyelinating, 2mutationwhole exome sequencingcentral nervous system diseasesMedicine (General)R5-920ENIranian Journal of Medical Sciences, Vol 46, Iss 6, Pp 493-497 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	leukodystrophy, hypomyelinating, 2 mutation whole exome sequencing central nervous system diseases Medicine (General) R5-920
spellingShingle	leukodystrophy, hypomyelinating, 2 mutation whole exome sequencing central nervous system diseases Medicine (General) R5-920 Sepehr Javadikooshesh Hooshang Zaimkohan Parisa Pourghorban Fatemeh Bahramim Nader Ebadi Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report
description	Pelizaeus-Merzbacher-Like Disease 1 is a genetic disorder affecting the central nervous system with an autosomal recessive inheritance pattern. It is a rare genetic disorder that affects the central nervous system. In this report, we demonstrated the clinical and paraclinical features of an Iranian consanguine pedigree with suspected hypomyelinating leukodystrophy, without any defined diagnosis. The proband, a 15-month-old girl, visited the Razi pathobiology and medical genetic laboratory of Karaj, where the study was conducted in 2020. Following whole-exome sequencing analysis of the proband and segregation analysis, a novel pathogenic mutation was discovered. GJC2 (NM_020435.4):c.1096dupG was found to be homozygous in the proband and heterozygous in both parents. This mutation was in the coding region of the protein, which results in D366Gfs*126 (p.Asp366GlyfsTer126). The site of mutation was at the 3’ region of the connexin superfamily domain. The frameshift results in a different peptide sequence of the C-terminal and extended protein. Our findings led to the diagnosis of the proband’s disease as Pelizaeus-Merzbacher-Like Disease 1 and led to the end of the diagnostic odyssey. We provided effective genetic counseling through the identification of a novel pathogenic mutation in gap junction protein C2 in this family and suggested preimplantation genetic diagnosis for the next pregnancy. Furthermore, our findings confirmed the association of GJC2 mutations with PMLD1. This discovery added to the repertoire of genetic mutations of Pelizaeus-Merzbacher-Like Disease 1. This knowledge could be applied for expanded carrier screening of other families, especially for Iranian consanguine marriages.
format	article
author	Sepehr Javadikooshesh Hooshang Zaimkohan Parisa Pourghorban Fatemeh Bahramim Nader Ebadi
author_facet	Sepehr Javadikooshesh Hooshang Zaimkohan Parisa Pourghorban Fatemeh Bahramim Nader Ebadi
author_sort	Sepehr Javadikooshesh
title	Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report
title_short	Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report
title_full	Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report
title_fullStr	Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report
title_full_unstemmed	Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report
title_sort	pelizaeus-merzbacher-like disease 1 caused by a novel mutation in gjc2 gene: a case report
publisher	Shiraz University of Medical Sciences
publishDate	2021
url	https://doaj.org/article/3ef2fd1a7b6e41edb1341fb032085209
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Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report

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