Myotonia congenita in a large consanguineous Arab family: Insight into the clinical spectrum of carriers and double heterozygotes of a novel mutation in the chloride channel CLCN1 gene

Adel Shalata, Haya Furman, Vardit Adir, Noam Adir, Yasir Hujeirat, Stavit A. Shalev, Zvi U. Borochowitz

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20 Scopus citations

Abstract

The aims of this study were to (1) characterize the clinical phenotype, (2) define the causative mutation, and (3) correlate the clinical phenotype with genotype in a large consanguineous Arab family with myotonia congenita. Twentyfour family members from three generations were interviewed and examined. Genomic DNA was extracted from peripheral blood samples for sequencing the exons of the CLCN1 gene. Twelve individuals with myotonia congenita transmitted the condition in an autosomal dominant manner with incomplete penetrance. A novel missense mutation [568GG>TC (G190S)] was found in a dose-dependent clinical phenotype. Although heterozygous individuals were asymptomatic or mildly affected, the homozygous individuals were severely affected. The mutation is a glycine-to-serine residue substitution in a well-conserved motif in helix D of the CLC-1 chloride channel in the skeletal muscle plasmalemma. A novel mutation, 568GG>TC (G190S) in the CLCN1 gene, is responsible for autosomal dominant myotonia congenita with a variable phenotypic spectrum.

Original languageEnglish
Pages (from-to)464-469
Number of pages6
JournalMuscle and Nerve
Volume41
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

Keywords

  • Autosomal dominant
  • CLCN1 gene
  • Mutation
  • Myotonia congenita

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