title: Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype.
abstract: Mutations in the CLCN1 gene, encoding a muscle-specific chloride channel, can cause either recessive or dominant myotonia congenita (MC). The recessive form, Becker's myotonia, is believed to be caused by two loss-of-function mutations, whereas the dominant form, Thomsen's myotonia, is assumed to be a consequence of a dominant-negative effect. However, a subset of CLCN1 mutations can cause both recessive and dominant MC. We have identified two recessive and two dominant MC families segregating the common R894X mutation. Real-time quantitative RT-PCR did not reveal any obvious association between the total CLCN1 mRNA level in muscle and the mode of inheritance, but the dominant family with the most severe phenotype expressed twice the expected amount of the R894X mRNA allele. Variation in allelic expression has not previously been described for CLCN1, and our finding suggests that allelic variation may be an important modifier of disease progression in myotonia congenita.
authors.affiliation: Department of Clinical Genetics, 4062, University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. mdunoe@rh.dk
authors.forename: Morten
authors.initials: M
authors.lastname: Dunø
authors.forename: Eskild
authors.initials: E
authors.lastname: Colding-Jørgensen
authors.forename: Morten
authors.initials: M
authors.lastname: Grunnet
authors.forename: Thomas
authors.initials: T
authors.lastname: Jespersen
authors.forename: John
authors.initials: J
authors.lastname: Vissing
authors.forename: Marianne
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000483:Alleles; D018118:Chloride Channels / Q000235:genetics*; D017931:DNA Primers; D015870:Gene Expression; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009224:Myotonia Congenita / Q000235:genetics*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; D017931:DNA Primers