Familial myopathy with desmin storage seen as a granulo-filamentar, electron-dense material with mutation of the alpha beta-cristallin gene

Two familial cases of a myopathy remarkable by the presence of a granulo-fi lamentar, electron dense material were reported in 1978. In a second step, in 1988, it was demonstrated that this material contained an abnormally-pho sphorylated desmin. During the last twenty years, the occurrence of new cas es in this family confirmed the autosomal dominant inheritance of the disea se, and made it potentially informative for molecular genetics studies. Thi s allowed first to map the disease on chromosome 11q21-23, and afterwards t o identify a mutation within a gene coding for a chaperone protein, alpha B crystallin. An extensive clinical, pathological and genetic study of this princeps fami ly is herein reported in detail. First, it showed the possible detection of histopathological changes in presymptomatic patients. Second, it allowed t o demonstrate the simultaneous occurrence of both alpha B crystallin and de smin in the granulo-filamentar aggregates. Third, this study provided a pre cise knowledge of the evolution rate of the disease. The analysis of simila r observations reported in the literature clearly shows the clinical, patho logical and genetic heterogeneity of this new neuro-muscular disorder.