Identification of five new mutations and three novel polymorphisms in the muscle chloride channel gene (CLCN1) in 20 Italian patients with dominant and recessive myotonia congenita. Mutations in brief no. 118. Online.

Autosomal dominant myotonia congenita or Thomsen's disease and autosomal recessive myotonia congenita or Becker's are rare nondystrophic disorders due to allelic mutations of the muscle chloride channel gene, CLCN1. We have analysed all 24 exons of the CLCN1 gene, in a panel of 20 unrelated patients (9 with dominant and 11 with recessive mytotonia congenita). We have found five novel mutations including two missense (V5631, F708L), one nonsense (C481X), one splicing (IVS19+2T->A), and one frameshift (2264delC), and also detected the recurrent R894X mutation. These account for 10 of the 22 recessive alleles examined, while no mutations were found in the dominant form. We report three novel polymorphisms (-134T/G, 898C/A and 2154T/C). Our results support high molecular heterogeneity of these myotonias in Italian population and provide new insight for the diagnosis and genetic counselling of these diseases.