LGMD1B is an autosomal dominantly inherited, slowly progressive
limb girdle muscular dystrophy, with age-related atrioventricular cardiac conduction disturbances and the absence of early
contractures. The disease has been linked to chromosome 1q11-q21. Within this locus another
muscular dystrophy, the autosomal dominant form of
Emery-Dreifuss muscular dystrophy (AD-EDMD) has recently been mapped and the corresponding gene identified. AD-ADMD is characterized by early
contractures of elbows and Achilles tendons and a humero-peroneal distribution of weakness combined with a
cardiomyopathy with conduction defects. The disease gene of AD-EDMD is LMNA which encodes
lamins A/C, two
proteins of the nuclear envelope. In order to identify whether or not
LGMD1B and AD-EDMD are allelic disorders, we carried out a search for mutations in the LMNA gene in patients with
LGMD1B. For this, PCR/SSCP/sequencing screening was carried out for the 12 exons of LMNA on
DNA samples of individuals from three
LGMD1B families that were linked to chromo-some 1q11-q21. Mutations were identified in all three
LGMD1B families: a missense mutation, a deletion of a
codon and a
splice donor site mutation, respectively. The three mutations were identified in all affected members of the corresponding families and were absent in 100 unrelated control subjects. The present identification of mutations in the LMNA gene in
LGMD1B demonstrates that
LGMD1B and AD-EDMD are allelic disorders. Further analysis of phenotype-genotype relationship will help to clarify the variability of the phenotype observed in these two
muscular dystrophies.