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Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder

Most internal organs in humans and other vertebrates exhibit striking left-right asymmetry in position and structure. Variation of normal organ positioning results in left-right asymmetry disorders and presents as internal organ reversal or randomization. Up to date, at least 82 genes have been iden...

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Autores principales: Yuan, Lamei, Yu, Xuehui, Xiao, Heng, Deng, Sheng, Xia, Hong, Xu, Hongbo, Yang, Yan, Deng, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10345202/
https://www.ncbi.nlm.nih.gov/pubmed/37457836
http://dx.doi.org/10.3389/fmolb.2023.1190162
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author Yuan, Lamei
Yu, Xuehui
Xiao, Heng
Deng, Sheng
Xia, Hong
Xu, Hongbo
Yang, Yan
Deng, Hao
author_facet Yuan, Lamei
Yu, Xuehui
Xiao, Heng
Deng, Sheng
Xia, Hong
Xu, Hongbo
Yang, Yan
Deng, Hao
author_sort Yuan, Lamei
collection PubMed
description Most internal organs in humans and other vertebrates exhibit striking left-right asymmetry in position and structure. Variation of normal organ positioning results in left-right asymmetry disorders and presents as internal organ reversal or randomization. Up to date, at least 82 genes have been identified as the causative genetic factors of left-right asymmetry disorders. This study sought to discover potential pathogenic variants responsible for left-right asymmetry disorder present in a Han-Chinese family using whole exome sequencing combined with Sanger sequencing. Novel compound heterozygous variants, c.5690A>G (p.Asn1897Ser) and c.7759G>A (p.Val2587Met), in the dynein axonemal heavy chain 1 gene (DNAH1), were found in the proband and absent in unaffected family members. Conservation analysis has shown that the variants affect evolutionarily conserved residues, which may impact the tertiary structure of the DNAH1 protein. The novel compound heterozygous variants may potentially bear responsibility for left-right asymmetry disorder, which results from a perturbation of left-right axis coordination at the earliest embryonic development stages. This study broadens the variant spectrum of left-right asymmetry disorders and may be helpful for genetic counseling and healthcare management for the diagnosed individual, and promotes a greater understanding of the pathophysiology.
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spelling pubmed-103452022023-07-15 Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder Yuan, Lamei Yu, Xuehui Xiao, Heng Deng, Sheng Xia, Hong Xu, Hongbo Yang, Yan Deng, Hao Front Mol Biosci Molecular Biosciences Most internal organs in humans and other vertebrates exhibit striking left-right asymmetry in position and structure. Variation of normal organ positioning results in left-right asymmetry disorders and presents as internal organ reversal or randomization. Up to date, at least 82 genes have been identified as the causative genetic factors of left-right asymmetry disorders. This study sought to discover potential pathogenic variants responsible for left-right asymmetry disorder present in a Han-Chinese family using whole exome sequencing combined with Sanger sequencing. Novel compound heterozygous variants, c.5690A>G (p.Asn1897Ser) and c.7759G>A (p.Val2587Met), in the dynein axonemal heavy chain 1 gene (DNAH1), were found in the proband and absent in unaffected family members. Conservation analysis has shown that the variants affect evolutionarily conserved residues, which may impact the tertiary structure of the DNAH1 protein. The novel compound heterozygous variants may potentially bear responsibility for left-right asymmetry disorder, which results from a perturbation of left-right axis coordination at the earliest embryonic development stages. This study broadens the variant spectrum of left-right asymmetry disorders and may be helpful for genetic counseling and healthcare management for the diagnosed individual, and promotes a greater understanding of the pathophysiology. Frontiers Media S.A. 2023-06-29 /pmc/articles/PMC10345202/ /pubmed/37457836 http://dx.doi.org/10.3389/fmolb.2023.1190162 Text en Copyright © 2023 Yuan, Yu, Xiao, Deng, Xia, Xu, Yang and Deng. 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 Molecular Biosciences
Yuan, Lamei
Yu, Xuehui
Xiao, Heng
Deng, Sheng
Xia, Hong
Xu, Hongbo
Yang, Yan
Deng, Hao
Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder
title Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder
title_full Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder
title_fullStr Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder
title_full_unstemmed Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder
title_short Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder
title_sort identification of novel compound heterozygous variants in the dnah1 gene of a chinese family with left-right asymmetry disorder
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10345202/
https://www.ncbi.nlm.nih.gov/pubmed/37457836
http://dx.doi.org/10.3389/fmolb.2023.1190162
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