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

被引:1
作者
Musa, Nurul Huda [1 ,2 ]
Thilakavathy, Karuppiah [1 ,3 ]
Mohamad, Nur Afiqah [4 ,5 ]
Kennerson, Marina L. [6 ,7 ]
Mat, Liyana Najwa Inche [4 ]
Loh, Wei Chao [4 ]
Rashid, Anna Misyail Abdul [4 ]
Baharin, Janudin [4 ]
Ibrahim, Azliza [4 ]
Sulaiman, Wan Aliaa Wan [4 ]
Hoo, Fan Kee [4 ]
Basri, Hamidon [4 ]
Khan, Abdul Hanif Khan Yusof [4 ]
机构
[1] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Serdang, Malaysia
[2] Univ Teknol MARA, Ctr Fdn Studies, Kampus Dengkil, Dengkil, Selangor, Malaysia
[3] Univ Putra Malaysia, Fac Med & Hlth Sci, Genet & Regenerat Res Grp, Serdang, Malaysia
[4] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Neurol, Serdang, Malaysia
[5] Lincoln Univ Coll, Ctr Fdn Studies, Fdn Sci, Petaling Jaya, Malaysia
[6] Univ Sydney, ANZAC Res Inst, Northcott Neurosci Lab, Fac Med & Hlth,Sydney Local Hlth Dist, Sydney, NSW, Australia
[7] Concord Hosp, Mol Med Lab, Concord, NSW, Australia
关键词
myotonia congenita; CLCN1; Thomsen disease; autosomal dominant; chloride channel; case report; MUTATIONS; GENE; CHANNELOPATHIES; EXPRESSION;
D O I
10.3389/fgene.2022.972007
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页数:9
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共 34 条
  • [1] HOMOZYGOSITY FOR DOMINANT MUTATIONS INCREASES SEVERITY OF MUSCLE CHANNELOPATHIES
    Arzel-Hezode, Marianne
    Sternberg, Damien
    Tabti, Nacira
    Vicart, Savine
    Goizet, Cyril
    Eymard, Bruno
    Fontaine, Bertrand
    Fournier, Emmanuel
    [J]. MUSCLE & NERVE, 2010, 41 (04) : 470 - 477
  • [2] Epigenetics in amyotrophic lateral sclerosis: a role for histone post-translational modifications in neurodegenerative disease
    Bennett, Seth A.
    Tanaz, Royena
    Cobos, Samantha N.
    Torrente, Mariana P.
    [J]. TRANSLATIONAL RESEARCH, 2019, 204 : 19 - 30
  • [3] Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood
    Buckley, Lauren
    Lacey, Michelle
    Ehrlich, Melanie
    [J]. EPIGENOMICS, 2016, 8 (01) : 13 - 31
  • [4] Channelopathies of Skeletal Muscle Excitability
    Cannon, Stephen C.
    [J]. COMPREHENSIVE PHYSIOLOGY, 2015, 5 (02) : 761 - 790
  • [5] DNA Methylation in the Diagnosis of Monogenic Diseases
    Cerrato, Flavia
    Sparago, Angela
    Ariani, Francesca
    Brugnoletti, Fulvia
    Calzari, Luciano
    Coppede, Fabio
    De Luca, Alessandro
    Gervasini, Cristina
    Giardina, Emiliano
    Gurrieri, Fiorella
    Lo Nigro, Cristiana
    Merla, Giuseppe
    Miozzo, Monica
    Russo, Silvia
    Sangiorgi, Eugenio
    Sirchia, Silvia M.
    Squeo, Gabriella Maria
    Tabano, Silvia
    Tabolacci, Elisabetta
    Torrente, Isabella
    Genuardi, Maurizio
    Neri, Giovanni
    Riccio, Andrea
    [J]. GENES, 2020, 11 (04)
  • [6] Phenotypic variability in myotonia congenita
    Colding-Jorgensen, E
    [J]. MUSCLE & NERVE, 2005, 32 (01) : 19 - 34
  • [7] CpG islands and the regulation of transcription
    Deaton, Aimee M.
    Bird, Adrian
    [J]. GENES & DEVELOPMENT, 2011, 25 (10) : 1010 - 1022
  • [8] Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype
    Duno, M
    Colding-Jorgensen, E
    Grunnet, M
    Jespersen, T
    Vissing, J
    Schwartz, M
    [J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2004, 12 (09) : 738 - 743
  • [9] Duno M., 2021, Myotonia congenita
  • [10] Epigenetic regulation of neural gene expression and neuronal function
    Feng, Jian
    Fouse, Shaun
    Fan, Guoping
    [J]. PEDIATRIC RESEARCH, 2007, 61 (05) : 58R - 63R