Targeted Next Generation Sequencing in patients with Myotonia Congenita

Myotonia Congenita (MC) is a nondystrophic skeletal muscle disease characterized by muscle stiffness, weakness, delayed skeletal relaxation and hypertrophic muscle. The disease can be inherited as dominant or recessive. More than 130 mutations in CLCN1 gene have been identified. We analyzed the entire coding region and exon-intron boundaries of the CLCN1 gene in 40 MC patients. Samples already Sanger-sequenced were successively evaluated by Next Generation Sequencing (NGS), on Ion Torrent PGM. Moreover, additional 15 patients were sequenced directly by NGS. NGS allowed us to identify all CLCN1 mutations except those located within exon 3, demonstrating a 96% of sensitivity. Due to primer design, one SNP (exactly rs7794560) also failed to be detected. Our results enlarge the spectrum of CLCN1 mutations and showed a novel approach for molecular analysis of MC. •We analyzed the entire coding region and exon-intron boundaries of the CLCN1 gene.•For the first time we use a NGS method in patients with Myotonia Congenita.•We analyzed on NGS 40 patients already Sanger-sequenced and 15 novel patients.•We found 7 novel CLCN1 mutations.