Proof of genetic heterogeneity in the proximal myotonic myopathy syndrome (PROMM) and its relationship to myotonic dystrophy type 2 (DM2)

Recently, myotonic dystrophy type 2 has been described as a separate diseas e entity that is distinctive from classical Steinert's disease since it lac ks a CTG repeat expansion on chromosome 19q. A gene locus for myotonic dyst rophy type 2 has been mapped to chromosome 3q. Independently, proximal myot onic myopathy has been recognized as yet another form of a multisystem myot onic disorder. Its relationship to myotonic dystrophy type 2 remains to be clarified. In our linkage study of 17 German proximal myotonic myopathy fam ilies nine of them mapped to the myotonic dystrophy type 2 locus (LOD score 18.9). However, two families with a typical proximal myotonic myopathy phe notype were excluded from this locus (LOD score - 7.4). These results confi rm genetic heterogeneity in the proximal myotonic myopathy syndrome. Furthe rmore. in the majority of the proximal myotonic myopathy families the disea se phenotype may be caused by allelic mutations in the putative myotonic dy strophy type 2 gene. (C) 2000 Elsevier Science B.V. All rights reserved.