[Clinical, genealogical and molecular genetic study of Emery-Dreifuss muscular dystrophy]

A search for emerin and lamin A/C (LMNA) mutations was performed in a group of 63 unrelated patients with probable Emery-Dreifuss muscular dystrophy (EDMD) and other MD's with concomitant dilated cardiomyopathy (DCMP). Four different emerin mutations and 7 LMNA mutations were found in unrelated patients. One emerin mutation and 2 LMNA mutations, one of the latter being found twice, have been registered earlier; the rest of the mutations are novel. All the patients with emerin mutations and 3 patients with LMNA mutations represented single cases while 4 LMNA-related cases were familial. De novo origin was proved for one emerin and 3 LMNA mutations. Apart from EDMD phenotypes, varying also in age at onset and severity, 2 cases of limb girdle MD type 1B were diagnosed. One patient with LMNA mutation and severe DCMP had subclinical signs of skeletal myopathy only. There was an overlap between DCMP type 1A and MD's. Autosomal dominant EDMD seems to be more common than "classic" X-linked EDMD. We found neither emerin nor LMNA mutations in a subset of families with EDMD-like phenotypes that may imply an existence of other genes causing similar disorders. Taking into account clinical variability of MD's caused by emerin and LMNA mutations, DNA diagnosis should not confine to the "classic" phenotype. DNA diagnosis of EDMD is important boht for medical genetic counseling and for patients' management: timely diagnosis of the disease allows one to prevent fatal cardiologic complications.