title: 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.
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. Twenty-four 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.
authors.affiliation: Simon Winter Institute for Human Genetics, B'nai-Zion Medical Center, P.O. Box 4940, Haifa, 31048, Israel. adel.shalata@b-zion.org.il
authors.forename: Adel
authors.initials: A
authors.lastname: Shalata
authors.forename: Haya
authors.initials: H
authors.lastname: Furman
authors.forename: Vardit
authors.initials: V
authors.lastname: Adir
authors.forename: Noam
authors.initials: N
authors.lastname: Adir
authors.forename: Yasir
authors.initials: Y
authors.lastname: Hujeirat
authors.forename: Stavit A
authors.initials: SA
authors.lastname: Shalev
authors.forename: Zvi U
authors.initials: ZU
authors.lastname: Borochowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D018912:Arabs / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009224:Myotonia Congenita / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels