G.P.136: Muscle channelopathies: Clinical and genetic features in a large cohort of Italian patients

Abstract

Skeletal muscle channelopathies are rare diseases, including non-dystrophic myotonia and periodic paralysis, which are associated with a great inter- and intrafamilial phenotypic variability, making challenging genotype-phenotype correlations. Hence studies on large populations of patients are needed. We included patients referred to Carlo Besta Neurological Institute molecular laboratory with a clinical diagnosis of periodic paralysis or nondystrophic myotonia and mutated in CLCN1, SCN4A, KCNJ2 or CACNA1S. We investigated 301 patients, among which 195 (64.3%) patients mutated in CLCN1 gene, 74 (24.6%) in SCN4A, 28 (9.3%) in CACNA1S and 4 (1.3%) in KCNJ2. We found 22 novel mutations: 8 in CLCN1 gene, 13 in SCN4A and 1 in CACNA1S. All the mutations detected in SCN4A, CACNA1S and KCNJ2 genes were missense, except for an unreported 9-nucleotide deletion in SCN4A. On the contrary CLCN1mutations were missense in 131/195 (67.2%) patients and remaining cases showed nonsense, splice site or deletion mutations. Our study confirms genetic heterogeneity of muscle channelopathies, although a relatively small number of mutations is responsible for most of the cases.