Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy

G Bonne, MRD Barletta, S Varnous, HM Bécane… - Nature …, 1999 - nature.com
G Bonne, MRD Barletta, S Varnous, HM Bécane, EH Hammouda, L Merlini, F Muntoni…
Nature genetics, 1999nature.com
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows
and Achilles tendons, slowly progressive muscle wasting and weakness, and a
cardiomyopathy with conduction blocks which is life-threatening 1. Two modes of
inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM
181350). EDMD-AD is clinically identical to the X-linked forms of the disease 2, 3, 4.
Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form 5, 6. We …
Abstract
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening 1. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease 2, 3, 4. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form 5, 6. We have mapped the locus for EDMD-AD to an 8-cM interval on chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype in four other small families was potentially linked to this locus. This region contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the nuclear lamina, lamins A and C, produced by alternative splicing 7, 8. We identified four mutations in LMNA that co-segregate with the disease phenotype in the five families: one nonsense mutation and three missense mutations. These results are the first identification of mutations in a component of the nuclear lamina as a cause of inherited muscle disorder. Together with mutations in EMD (Refs 5, 6), they underscore the potential importance of the nuclear envelope components in the pathogenesis of neuromuscular disorders.
nature.com