Novel chloride channel gene mutations in two unrelated Japanese families with Becker's autosomal recessive generalized myotonia

We investigated the skeletal muscle voltage-gated chloride channel gene (CL CN1) in two unrelated Japanese patients with Becker's myotonia congenita. T he non-myotonic parents of each patient were consanguineous. The proband of each family shares generalized myotonia, transient weakness after rest, an d leg muscle hypertrophy. However, the disease severity related to the degr ee of myotonia differed, even in view of the response to long train nerve s timulation tests. CLCN1 gene analysis revealed a novel Ala659Val missense m utation identified to be homozygous in the more severe patient, while a nov el Gln445Stop nonsense mutation was present in the other patient. Both muta tions were absent in 90 Japanese normal controls. This is the first report of Japanese cases of Becker's myotonia congenita with CLCN1 gene mutations. (C) 1999 Elsevier Science B.V. All rights reserved.