Cargando…

Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family

Myotonia congenita (MC) is a rare neuromuscular disease caused by mutations within the CLCN1 gene encoding skeletal muscle chloride channels. MC is characterized by delayed muscle relaxation during contraction, resulting in muscle stiffness. There is a lack of MC case reports and data on the prevale...

Descripción completa

Detalles Bibliográficos
Autores principales: Musa, Nurul Huda, Thilakavathy, Karuppiah, Mohamad, Nur Afiqah, Kennerson, Marina L., Inche Mat, Liyana Najwa, Loh, Wei Chao, Abdul Rashid, Anna Misyail, Baharin, Janudin, Ibrahim, Azliza, Wan Sulaiman, Wan Aliaa, Hoo, Fan Kee, Basri, Hamidon, Yusof Khan, Abdul Hanif Khan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842662/
https://www.ncbi.nlm.nih.gov/pubmed/36659963
http://dx.doi.org/10.3389/fgene.2022.972007
_version_ 1784870189555253248
author Musa, Nurul Huda
Thilakavathy, Karuppiah
Mohamad, Nur Afiqah
Kennerson, Marina L.
Inche Mat, Liyana Najwa
Loh, Wei Chao
Abdul Rashid, Anna Misyail
Baharin, Janudin
Ibrahim, Azliza
Wan Sulaiman, Wan Aliaa
Hoo, Fan Kee
Basri, Hamidon
Yusof Khan, Abdul Hanif Khan
author_facet Musa, Nurul Huda
Thilakavathy, Karuppiah
Mohamad, Nur Afiqah
Kennerson, Marina L.
Inche Mat, Liyana Najwa
Loh, Wei Chao
Abdul Rashid, Anna Misyail
Baharin, Janudin
Ibrahim, Azliza
Wan Sulaiman, Wan Aliaa
Hoo, Fan Kee
Basri, Hamidon
Yusof Khan, Abdul Hanif Khan
author_sort Musa, Nurul Huda
collection PubMed
description Myotonia congenita (MC) is a rare neuromuscular disease caused by mutations within the CLCN1 gene encoding skeletal muscle chloride channels. MC is characterized by delayed muscle relaxation during contraction, resulting in muscle stiffness. There is a lack of MC case reports and data on the prevalence among Malaysians. We report a clinical case of a 50-year-old woman presents with muscle stiffness and cramp episodes that started in early childhood. She had difficulty initiating muscle movement and presented with transient muscle weakness after rest, which usually improved after repeated contraction (warm-up phenomenon). She was diagnosed with MC after myotonic discharge on electromyography (EMG). Her brother had similar symptoms; however, no additional family members showed MC symptoms. Serum creatine kinase levels were elevated in both the proband and her brother with 447 U/L and 228 U/L recorded, respectively. Genetic analysis by whole-exome sequencing (WES) revealed a previously reported pathogenic CLCN1 gene variant c.1667T>A (p.I556N). Genetic screening of all family members revealed that the same variant was observed in the children of both the proband and her brother; however, the children did not present with either clinical or electrophysiological MC symptoms. The multiplex ligation-dependent probe amplification (MLPA) analysis conducted identified neither exon deletion nor duplication in CLCN1. In conclusion, this report describes the first case of MC in Malaysia in which incomplete penetrance observed in this family is caused by a known pathogenic CLCN1 variant.
format Online
Article
Text
id pubmed-9842662
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-98426622023-01-18 Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family Musa, Nurul Huda Thilakavathy, Karuppiah Mohamad, Nur Afiqah Kennerson, Marina L. Inche Mat, Liyana Najwa Loh, Wei Chao Abdul Rashid, Anna Misyail Baharin, Janudin Ibrahim, Azliza Wan Sulaiman, Wan Aliaa Hoo, Fan Kee Basri, Hamidon Yusof Khan, Abdul Hanif Khan Front Genet Genetics Myotonia congenita (MC) is a rare neuromuscular disease caused by mutations within the CLCN1 gene encoding skeletal muscle chloride channels. MC is characterized by delayed muscle relaxation during contraction, resulting in muscle stiffness. There is a lack of MC case reports and data on the prevalence among Malaysians. We report a clinical case of a 50-year-old woman presents with muscle stiffness and cramp episodes that started in early childhood. She had difficulty initiating muscle movement and presented with transient muscle weakness after rest, which usually improved after repeated contraction (warm-up phenomenon). She was diagnosed with MC after myotonic discharge on electromyography (EMG). Her brother had similar symptoms; however, no additional family members showed MC symptoms. Serum creatine kinase levels were elevated in both the proband and her brother with 447 U/L and 228 U/L recorded, respectively. Genetic analysis by whole-exome sequencing (WES) revealed a previously reported pathogenic CLCN1 gene variant c.1667T>A (p.I556N). Genetic screening of all family members revealed that the same variant was observed in the children of both the proband and her brother; however, the children did not present with either clinical or electrophysiological MC symptoms. The multiplex ligation-dependent probe amplification (MLPA) analysis conducted identified neither exon deletion nor duplication in CLCN1. In conclusion, this report describes the first case of MC in Malaysia in which incomplete penetrance observed in this family is caused by a known pathogenic CLCN1 variant. Frontiers Media S.A. 2023-01-03 /pmc/articles/PMC9842662/ /pubmed/36659963 http://dx.doi.org/10.3389/fgene.2022.972007 Text en Copyright © 2023 Musa, Thilakavathy, Mohamad, Kennerson, Inche Mat, Loh, Abdul Rashid, Baharin, Ibrahim, Wan Sulaiman, Hoo, Basri and Yusof Khan. 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
Musa, Nurul Huda
Thilakavathy, Karuppiah
Mohamad, Nur Afiqah
Kennerson, Marina L.
Inche Mat, Liyana Najwa
Loh, Wei Chao
Abdul Rashid, Anna Misyail
Baharin, Janudin
Ibrahim, Azliza
Wan Sulaiman, Wan Aliaa
Hoo, Fan Kee
Basri, Hamidon
Yusof Khan, Abdul Hanif Khan
Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family
title Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family
title_full Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family
title_fullStr Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family
title_full_unstemmed Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family
title_short Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family
title_sort case report: incomplete penetrance of autosomal dominant myotonia congenita caused by a rare clcn1 variant c.1667t>a (p.i556n) in a malaysian family
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842662/
https://www.ncbi.nlm.nih.gov/pubmed/36659963
http://dx.doi.org/10.3389/fgene.2022.972007
work_keys_str_mv AT musanurulhuda casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT thilakavathykaruppiah casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT mohamadnurafiqah casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT kennersonmarinal casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT inchematliyananajwa casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT lohweichao casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT abdulrashidannamisyail casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT baharinjanudin casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT ibrahimazliza casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT wansulaimanwanaliaa casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT hoofankee casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT basrihamidon casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily
AT yusofkhanabdulhanifkhan casereportincompletepenetranceofautosomaldominantmyotoniacongenitacausedbyarareclcn1variantc1667tapi556ninamalaysianfamily