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Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal–Distal Myopathy in a Chinese Patient

DNAJB6 was identified as the causative gene of limb-girdle muscular dystrophy type 1D. In recent years, the phenotypic and molecular spectrum of DNAJB6-myopathy has been expanded, and several mutations of DNAJB6 have been identified in Europe, North America, and Asia. Interestingly, almost all ident...

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Autores principales: Ji, Guang, Wang, Ning, Han, Xu, Wang, Yaye, Zhang, Jinru, Wu, Yue, Wu, Hongran, Ma, Shaojuan, Song, Xueqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259785/
https://www.ncbi.nlm.nih.gov/pubmed/35812750
http://dx.doi.org/10.3389/fgene.2022.925926
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author Ji, Guang
Wang, Ning
Han, Xu
Wang, Yaye
Zhang, Jinru
Wu, Yue
Wu, Hongran
Ma, Shaojuan
Song, Xueqin
author_facet Ji, Guang
Wang, Ning
Han, Xu
Wang, Yaye
Zhang, Jinru
Wu, Yue
Wu, Hongran
Ma, Shaojuan
Song, Xueqin
author_sort Ji, Guang
collection PubMed
description DNAJB6 was identified as the causative gene of limb-girdle muscular dystrophy type 1D. In recent years, the phenotypic and molecular spectrum of DNAJB6-myopathy has been expanded, and several mutations of DNAJB6 have been identified in Europe, North America, and Asia. Interestingly, almost all identified mutations in previous reports were point mutations, and most of them were clustered in exon 5, which encodes the G/F domain of DNAJB6. The so-far unique splice site mutation eliminating the entire G/F domain was reported to cause a severe, early-onset phenotype. Here, we report a juvenile-onset Chinese patient who presented with proximal–distal myopathy as well as esotropia and facial weakness. Muscle pathology showed rimmed vacuolation and myofibrillar disarrangement. A novel splice-site mutation NM_058246:c.236-1_240delGGTGGA of the DNAJB6 gene was identified by targeted exome sequencing, which results in a severe defect of the G/F domain. This rare mutation type expands the molecular spectrum of DNAJB6-myopathy and further underlines the importance of the G/F region.
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spelling pubmed-92597852022-07-08 Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal–Distal Myopathy in a Chinese Patient Ji, Guang Wang, Ning Han, Xu Wang, Yaye Zhang, Jinru Wu, Yue Wu, Hongran Ma, Shaojuan Song, Xueqin Front Genet Genetics DNAJB6 was identified as the causative gene of limb-girdle muscular dystrophy type 1D. In recent years, the phenotypic and molecular spectrum of DNAJB6-myopathy has been expanded, and several mutations of DNAJB6 have been identified in Europe, North America, and Asia. Interestingly, almost all identified mutations in previous reports were point mutations, and most of them were clustered in exon 5, which encodes the G/F domain of DNAJB6. The so-far unique splice site mutation eliminating the entire G/F domain was reported to cause a severe, early-onset phenotype. Here, we report a juvenile-onset Chinese patient who presented with proximal–distal myopathy as well as esotropia and facial weakness. Muscle pathology showed rimmed vacuolation and myofibrillar disarrangement. A novel splice-site mutation NM_058246:c.236-1_240delGGTGGA of the DNAJB6 gene was identified by targeted exome sequencing, which results in a severe defect of the G/F domain. This rare mutation type expands the molecular spectrum of DNAJB6-myopathy and further underlines the importance of the G/F region. Frontiers Media S.A. 2022-06-23 /pmc/articles/PMC9259785/ /pubmed/35812750 http://dx.doi.org/10.3389/fgene.2022.925926 Text en Copyright © 2022 Ji, Wang, Han, Wang, Zhang, Wu, Wu, Ma and Song. 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
Ji, Guang
Wang, Ning
Han, Xu
Wang, Yaye
Zhang, Jinru
Wu, Yue
Wu, Hongran
Ma, Shaojuan
Song, Xueqin
Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal–Distal Myopathy in a Chinese Patient
title Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal–Distal Myopathy in a Chinese Patient
title_full Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal–Distal Myopathy in a Chinese Patient
title_fullStr Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal–Distal Myopathy in a Chinese Patient
title_full_unstemmed Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal–Distal Myopathy in a Chinese Patient
title_short Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal–Distal Myopathy in a Chinese Patient
title_sort case report: a novel splice-site mutation in dnajb6 associated with juvenile-onset proximal–distal myopathy in a chinese patient
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259785/
https://www.ncbi.nlm.nih.gov/pubmed/35812750
http://dx.doi.org/10.3389/fgene.2022.925926
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