Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia

Lorenzo Maggi, Sabrina Ravaglia, Alessandro Farinato, Raffaella Brugnoni, Concetta Altamura, Paola Imbrici, Diana Conte Camerino, Alessandro Padovani, Renato Mantegazza, Pia Bernasconi, Jean François Desaphy, Massimiliano Filosto

Research output: Contribution to journalArticlepeer-review


Non-dystrophic myotonias are characterized by clinical overlap making it challenging to establish genotype-phenotype correlations. We report clinical and electrophysiological findings in a girl and her father concomitantly harbouring single heterozygous mutations in SCN4A and CLCN1 genes. Functional characterization of N1297S hNav1.4 mutant was performed by patch clamp. The patients displayed a mild phenotype, mostly resembling a sodium channel myotonia. The CLCN1 c.501C>G (p.F167L) mutation has been already described in recessive pedigrees, whereas the SCN4A c.3890A>G (p.N1297S) variation is novel. Patch clamp experiments showed impairment of fast and slow inactivation of the mutated Nav1.4 sodium channel. The present findings suggest that analysis of both SCN4A and CLCN1 genes should be considered in myotonic patients with atypical clinical and neurophysiological features.

Original languageEnglish
Pages (from-to)219-225
Number of pages7
Issue number4
Publication statusPublished - Dec 1 2017


  • CLCN1 gene
  • Congenital myotonia
  • Patch clamp
  • SCN4A gene
  • Skeletal muscle channelopathies

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience


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