TY - JOUR
T1 - Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia
AU - Maggi, Lorenzo
AU - Ravaglia, Sabrina
AU - Farinato, Alessandro
AU - Brugnoni, Raffaella
AU - Altamura, Concetta
AU - Imbrici, Paola
AU - Camerino, Diana Conte
AU - Padovani, Alessandro
AU - Mantegazza, Renato
AU - Bernasconi, Pia
AU - Desaphy, Jean François
AU - Filosto, Massimiliano
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - CLCN1 gene
KW - Congenital myotonia
KW - Patch clamp
KW - SCN4A gene
KW - Skeletal muscle channelopathies
UR - http://www.scopus.com/inward/record.url?scp=85030863058&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030863058&partnerID=8YFLogxK
U2 - 10.1007/s10048-017-0525-5
DO - 10.1007/s10048-017-0525-5
M3 - Article
AN - SCOPUS:85030863058
SN - 1364-6745
VL - 18
SP - 219
EP - 225
JO - Neurogenetics
JF - Neurogenetics
IS - 4
ER -