title: Dosage effect of a dominant CLCN1 mutation: a novel syndrome.
abstract: Multiple mutations in the CLCN1 gene coding for the voltage-gated chloride channel have been documented to cause myotonia congenita. We report a kindred featuring an index patient who possesses 2 copies of a dominantly inherited mutated CLCN1 allele with a resulting novel phenotypic presentation. The index patient is a boy who presented initially for evaluation at the age of 5 years with a 2-year history of gait problems. Both parents and 3 male siblings were entirely well. Examination revealed a striking diffuse muscular hypertrophy, diffuse mild to moderate weakness, Gower sign, percussion, and grip myotonia. Electromyography confirmed myotonia, and molecular analysis revealed 2 copies of the T310M mutation on the CLCN1 gene. Testing of family members revealed a normal neurological examination without clinical myotonia in all and electromyographic evidence of myotonia and a single copy of the T310M mutation in both parents and 2 siblings. Our kindred is the initial demonstration of the dosage effect of a dominant mutated allele in the CLCN1 gene.
authors.affiliation: Department of Neurology/Neurosurgery, McGill University Health Center, Montreal, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bernard
authors.forename: Chantal
authors.initials: C
authors.lastname: Poulin
authors.forename: Jack
authors.initials: J
authors.lastname: Puymirat
authors.forename: Damien
authors.initials: D
authors.lastname: Sternberg
authors.forename: Michael
authors.initials: M
authors.lastname: Shevell
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004576:Electromyography; D018628:Gene Dosage; D005799:Genes, Dominant; D018737:Hand Strength; D006801:Humans; D006984:Hypertrophy / Q000235:genetics; D008297:Male; D018908:Muscle Weakness / Q000235:genetics / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D009224:Myotonia Congenita / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D013577:Syndrome
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels