Founder mutations and the high prevalence of myotonia congenita in northern Finland.

Objective And Background: To find an explanation at the molecular level for the high prevalence of myotonia congenita in northern Finland and the exceptional pattern of inheritance of the disease in many families, and to study genotype-phenotype correlation in the patients.

Methods: Forty-six patients with myotonia congenita and 16 unaffected relatives from 24 families were studied. All 23 exons and their flanking regions of the gene for the chloride channel protein (ClC-1) were sequenced from at least one patient from all families.

Duplication of seven exons in the lysyl hydroxylase gene is associated with longer forms of a repetitive sequence within the gene and is a common cause for the type VI variant of Ehlers-Danlos syndrome.

The type VI variant of the Ehlers-Danlos syndrome (EDS) is a recessively inherited connective tissue disorder which, in most families, is due to a deficiency in lysyl hydroxylase activity. We have recently characterized a homozygous duplication of 8.9 kb in the lysyl hydroxylase gene (PLOD) in two EDS VI families.