Linkage and mutation analysis of Thomsen and Becker myotonia families
- Univ. of Pittsburgh, PA (United States); and others
Thomsen (autosomal dominant) and Becker (autosomal recessive) myotonias are characterized by the inability for muscle relaxation after voluntary, mechanical, or electrical stimulation. Families with both diseases have been linked to the skeletal muscle chloride channel (CLC1) on chromosome 7q35; however, only 2 gene mutations have been identified, and the reasons underlying the alternative dominant or recessive inheritance are not clear. We used linkage analysis and SSCP of 23 exons to screen 8 families (56 individuals) and 7 isolated cases with the diagnosis of Thomsen/Becker myotonia. A novel mutation (1290M) in exon 8 was detected in a family with Thomsen disease. Three additional families showed the previously described G230E change. Thus, chloride channel mutations could be identified in 4/5 families showing dominant inheritance. We were able to exclude linkage to the CLC1 gene in the fifth family. In patients with recessive Becker disease, an isolated case had two unique conformers, one causing a novel A437T change in exon 12. We also identified the previously reported F413C change in a second family. We found significant differences in the clinical picture between families with different mutations but also in families with the same mutation. Our data indicates that DNA studies are critical for correct diagnosis of the myotonias.
- OSTI ID:
- 134237
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
Similar Records
Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome 7q35
Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia