UvA-DARE ( Digital Academic Repository ) Collagen VI mutations in Bethlem myopathy

Bethlem myopathy is a rare autosomal dominant myopathy characterized by slowly progressive limb-girdle muscular atrophy and weakness, and contractures of multiple joints. To identify the genetic localization we used highly polymorphic microsatellite markers in a genome-wide search in six Dutch families. After excluding genetic linkage with 52 markers distributed evenly over the autosomes, significant linkage was present with the 21q22.3 locus PFKL (two-point lod score of Zmax = 6.86 at 0 = 0.03). There was no indication of genetic heterogeneity. The pattern of recombinations observed with adjacent markers indicated a localization distal to PFKL. Recombination of a marker within the collagen al(VI) gene (COL6A1) excluded this apparent candidate gene in one of the Bethlem myopathy families. The disease gene is most likely located in the region between COL6A1 and the telomere of chromosome 21q.