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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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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 |
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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 |
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