title: Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene.
abstract: Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle. We have studied 48 families with myotonia, 32 out of them carrying mutations in CLCN1 gene and eight carry mutations in SCN4A gene. We have found 26 different mutations in CLCN1 gene, including 13 not reported previously. Among those 26 mutations, c.180+3A>T in intron 1 is present in nearly one half of the Spanish families in this series, the largest one analyzed in Spain so far. Although scarce data have been published on the frequency of mutation c.180+3A>T in other populations, our data suggest that this mutation is more frequent in Spain than in other European populations. In addition, expression in HEK293 cells of the new missense mutants Tyr137Asp, Gly230Val, Gly233Val, Tyr302His, Gly416Glu, Arg421Cys, Asn567Lys and Gln788Pro, demonstrated that these DNA variants are disease-causing mutations that abrogate chloride currents.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Departamento de Bioquímica, CSIC-UAM, Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Mazón
authors.forename: Francisco
authors.initials: F
authors.lastname: Barros
authors.forename: Pilar
authors.initials: P
authors.lastname: De la Peña
authors.forename: Juan F
authors.initials: JF
authors.lastname: Quesada
authors.forename: Adela
authors.initials: A
authors.lastname: Escudero
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cobo
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Pascual-Pascual
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gutiérrez-Rivas
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillén
authors.forename: Javier
authors.initials: J
authors.lastname: Arpa
authors.forename: Pilar
authors.initials: P
authors.lastname: Eraso
authors.forename: Francisco
authors.initials: F
authors.lastname: Portillo
authors.forename: Jesús
authors.initials: J
authors.lastname: Molano
mesh_terms: D000293:Adolescent; D000328:Adult; D055592:Biophysical Phenomena / Q000235:genetics; D001703:Biophysics; D002461:Cell Line, Transformed; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D004558:Electric Stimulation; D004576:Electromyography; D005192:Family Health; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics*; D009222:Myotonia / Q000175:diagnosis* / Q000235:genetics*; D018408:Patch-Clamp Techniques; D013030:Spain; D014162:Transfection; D055815:Young Adult
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels