Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene

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• 作者：Marí ; a J. Mazó ; n^a ; Francisco Barros^b ; Pilar De la Peñ ; a^b ; Juan F. Quesada^c ; Adela Escudero^c ; Ana M. Cobo^d ; ¹ ; Samuel I. Pascual-Pascual^e ; Eduardo Guti&#233 ; rrez-Rivas^f ; Encarna Guill&#233 ; n^g ; Javier Arpa^h ; Pilar Eraso^a ; Francisco Portillo^a ; Jesú ; s Molano^c ; ^{jmolano.hulp@salud.madrid.org}
• 关键词：Myotonia congenita ; Thomsen disease ; Becker&rsquo ; s disease ; CLCN1 mutations ; Functional analysis
• 刊名：Neuromuscular Disorders
• 出版年：2012
• 期刊代码：203_09608966
• 类别：med
• 出版时间：March, 2012
• 卷：22
• 期：3
• 页码：231-243
• 文件大小：805 K

摘要

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.