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

Autor:	Musa NH; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.; Centre of Foundation Studies, Universiti Teknologi MARA, Cawangan Selangor, Kampus Dengkil, Dengkil, Selangor, Malaysia., Thilakavathy K; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.; Genetics and Regenerative Research Group, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Mohamad NA; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.; Center for Foundation Studies, Foundation in Science, Lincoln University College, Petaling Jaya, Malaysia., Kennerson ML; Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney Local Health District, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Molecular Medicine Laboratory, Concord Hospital, Concord, NSW, Australia., Inche Mat LN; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Loh WC; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Abdul Rashid AM; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Baharin J; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Ibrahim A; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Wan Sulaiman WA; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Hoo FK; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Basri H; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia., Yusof Khan AHK; Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2023 Jan 03; Vol. 13, pp. 972007. Date of Electronic Publication: 2023 Jan 03 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.972007
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Musa, Thilakavathy, Mohamad, Kennerson, Inche Mat, Loh, Abdul Rashid, Baharin, Ibrahim, Wan Sulaiman, Hoo, Basri and Yusof Khan.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu