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09.10.2017 | Original Article

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

verfasst von: 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

Erschienen in: Neurogenetics | Ausgabe 4/2017

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Abstract

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.

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Titel: Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia
verfasst von: 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
Publikationsdatum: 09.10.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Neurogenetics / Ausgabe 4/2017
Print ISSN: 1364-6745
Elektronische ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-017-0525-5

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