RESUMO
Myotonia congenita (MC) is a Mendelian inherited genetic disease caused by the mutations in the CLCN1 gene, encoding the main skeletal muscle ion chloride channel (ClC-1). The clinical diagnosis of MC should be suspected in patients presenting myotonia, warm-up phenomenon, a characteristic electromyographic pattern, and/or family history. Here, we describe the largest cohort of MC Spanish patients including their relatives (up to 102 individuals). Genetic testing was performed by CLCN1 sequencing and multiplex ligation-dependent probe amplification (MLPA). Analysis of selected exons of the SCN4A gene, causing paramyotonia congenita, was also performed. Mutation spectrum and analysis of a likely founder effect of c.180+3A>T was achieved by haplotype analysis and association tests. Twenty-eight different pathogenic variants were found in the CLCN1 gene, of which 21 were known mutations and seven not described. Gross deletions/duplications were not detected. Four probands had a pathogenic variant in SCN4A. Two main haplotypes were detected in c.180+3A>T carriers and no statistically significant differences were detected between case and control groups regarding the type of haplotype and its frequencies. A diagnostic yield of 51% was achieved; of which 88% had pathogenic variants in CLCN1 and 12% in SCN4A. The existence of a c.180+3A>T founder effect remains unsolved.