IDENTIFICATION OF NEW MUTATIONS IN THE EMERY-DREIFUSS MUSCULAR-DYSTROPHY GENE AND EVIDENCE FOR GENETIC-HETEROGENEITY OF THE DISEASE

The Emery-Dreifuss Muscular Dystrophy (EDMD) is an X-linked recessive muscular disorder characterized by early contractures of the elbows, A chilles tendons and postcervical muscles, slowly progressing muscle wa sting and weakness and a cardiomyopathy characterized by conduction de fects. Heart block is a frequent cause of death. Finding of mutations in one of the transcripts in the critical region in distal Xq28 led to the identification of the gene responsible for the disease. We now re port the sequence of the gene which is 2100 bp long and the developmen t of a set of primers to amplify and sequence the gene from patients' DNA. Eight unrelated X-linked familial cases were studied and they all carried different mutations, showing that lack of emerin in cardiac a nd skeletal muscle is the cause of the X-linked disease. No mutations were found in a family where the female carrier was affected nor in a sporadic case with a well established diagnosis of EDMD. Our findings suggest genetic heterogeneity of EDMD, and that at least two genes, th e X-linked STA gene and one unidentified autosomal gene, are responsib le for the disease.