1) We found that familial cardiac and skeletal myopathy characterized by accumulation of desmin deposits in muscle cells is associated with mutations in the desmin gene. A heterozygous A337P mutation was identified in a family with late onset slowly progressive skeletal myopathy with mild cardiac involvement. Compound heterozygosity for two other mutations, A360P and N393I, was detected in a second family characterized by childhood onset and aggressive course of cardiac and skeletal myopathy. SW13-minus cells expressing each of these mutations suffer complete destruction of desmin network and accumulation of granular desmin-positive deposits. In-vitro experiments confirmed pathogenic potentials of the mutations we have identified in our patients. 2) Two separate disorders, distal spinal muscular atrophy type V (dSMA-V) and Charcot-Marie-Tooth disease type 2D (CMT2D) were diagnosed in a single large kindred. Multipoint lod score of 6.07 suggested that the gene for both syndromes is located between markers D7S526 and D7S474. A conserved disease-associ- ated haplotype was established in affected individuals suffering from either disorder. Based on informative recombination events, the disease locus was placed within a 3 cM interval between markers D7S2496 and D7S1514 within the 7p15 band. Data obtained from this study suggest that a single gene is responsible for both syndromes, dSMA-V and CMT2D, increase the resolution of the candidate locus and facilitate the search for the gene.
