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Identification of three novel mutations in the major human skeletal muscle chloride channel gene (CLCN1), causing myotonia congenita
Author(s) -
Brugi Raffaella,
Galantini Stefania,
Confalonieri Paolo,
Balestrini Maria Rosa,
Cornelio Ferdinando,
Mantegazza Renato
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(199911)14:5<447::aid-humu13>3.0.co;2-z
Subject(s) - missense mutation , exon , myotonia , myotonia congenita , biology , genetics , skeletal muscle , exon skipping , mutation , gene , microbiology and biotechnology , endocrinology , alternative splicing , myotonic dystrophy
Myotonia congenita (MC) is a genetic disease characterized by mutations in the CLCN1 gene (OMIM*118425) encoding the skeletal muscle voltage‐gated chloride channel (ClC‐1). Autosomal dominant and recessive forms are observed, characterized by impaired muscle relaxation after forceful contraction (myotonia), which is more pronounced after inactivity and improves with exercise. We report three novel and one known mutations of the CLCN1 gene in four unrelated MC families. In two families the mutations were missense: 803C>T (T268M) and 1272C>G (I424M) in exons 7 and 12, respectively. The third was a splice mutation in intron 5 (696+2T>A), which induced a frame shift with a stop codon in exon 6 (fs213X). In the fourth family the previously‐reported missense mutation 689G>A (G230E) was found. We also report two known polymorphisms: 261C>T (T87T) and 2154T>C (D718D) in exons 2 and 17 of two MC families; also found in 14 (33%) and 28 (67%) of 42 healthy controls, respectively. These findings expand our knowledge of mutations responsible for myotonia congenita, reducing the proportion of MC patients in whom genetic alterations have not been found. Hum Mutat 14:447, 1999. © 1999 Wiley‐Liss, Inc.