TY - JOUR

T1 - Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype.

AU - Dunø, Morten

AU - Colding-Jørgensen, Eskild

AU - Grunnet, Morten

AU - Jespersen, Thomas

AU - Vissing, John

AU - Schwartz, Marianne

N1 - Keywords: Alleles; Chloride Channels; DNA Primers; Gene Expression; Humans; Inheritance Patterns; Muscle, Skeletal; Mutation; Myotonia Congenita; Pedigree; Reverse Transcriptase Polymerase Chain Reaction

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1038/sj.ejhg.5201218

DO - 10.1038/sj.ejhg.5201218

M3 - Journal article

C2 - 15162127

VL - 12

SP - 738

EP - 743

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 9

ER -