title: Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).
abstract: 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.
authors.affiliation: INSERM UR523, Institut de Myologie, GH Pitié-Salpétrière, 75013 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Muchir
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: M
authors.initials: M
authors.lastname: van Meegen
authors.forename: F
authors.initials: F
authors.lastname: Baas
authors.forename: P A
authors.initials: PA
authors.lastname: Bolhuis
authors.forename: M
authors.initials: M
authors.lastname: de Visser
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D003062:Codon; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005192:Family Health; D017353:Gene Deletion; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D007438:Introns; D034882:Lamins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D017386:Sequence Homology, Amino Acid
chemical_list: D003062:Codon; D018076:DNA, Complementary; D034882:Lamins; D009687:Nuclear Proteins