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Aim. To describe the clinical variability of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) with cardiac involvement in a four-generation family with a novel mutation in STA gene. Methods. Clinical data were provided for 4 affected males and female carrier. The Western blot analysis of emerin was performed on lymphoblastoid cell lines and followed by sequencing of the emerin gene. Result. A thyamine insertion at nucleotide 417 in exon 2, resulting in a frameshift with a premature stop codon at position 62 and absence of functional protein, was found in one of three avaliable patients. In ten-year-old proband's dizygotic twin-nephews the intermittent first-degree A-V block, atrial and ventricular ectopy, atrial runs, and exit sinus block were found, although the echocardiographic findings were normal. One of the twins also had short episodes of atrial fibrillation, idioventricular rhythm, and junctional rhythm. Conclusion Cardiac abnormalities in the proband's ten-year-old dizygotic twins without evident clinical features suggestive of EDMD were remarkable in contrast to the oldest patient in the family, who lived to the age of 63 without pacemaker, and to the proband who had a very early onset of muscular wasting and weaknes, and a pacemaker implantation at the age of 27. This striking intra-familial variability in cardiac involvement associated with specific null mutation (417 ins T)has practical early diagnostic and possibly preventive implications. It als points at genetic and environmental factors as cause of clinical features in X-EDMD.

Autosomal recessive limb-girdle muscular dystrophies (LGMD2) form a group of muscle diseases presenting great clinical and genetic heterogeneity. They are characterized by progressive muscular atrophy and weakness of the pelvic and shoulder girdle and proximal limb muscles, showing considerable variation in age of onset, evolution, and severity. At least six distinct genetic entities leading to an LGMD2 have been identified in the last years. They include four genes encoding for the sarcoglycans, the gene encoding for the calpain 3 (LGMD2A) and the LGMD2B locus mapped on chromosome 2p. We report seven males (two already deceased) and two females affected by a muscular dystrophy, similar to the description of juvenile limb-girdle muscular dystrophy of Reunion Island (Fardeau et al. Brain, 1996 ; 119: 295). A detailed clinical and genealogical study of these 9 patients from five apperently non related families permitted to identify links between the different nuclear families. Preliminary results of molecular analysis obtained by DGGE in two families have revealed three homozygous patients (oncle and his niece in one family ; one of two brothers in the second ) for the mutation 551 A. Because of increased inbreeding, we suspect that the same mutation is the cause of LGMD in other families as the consequence of founder effect in this village.