TY - JOUR
T1 - Mutations in the gene encoding lamin A/C cause autosomal dominant Emery- Dreifuss muscular dystrophy
AU - Bonne, Gisèle
AU - Di Barletta, Marina Raffaele
AU - Varnous, Shaida
AU - Bécane, Henri Marc
AU - Hammouda, El Hadi
AU - Merlini, Luciano
AU - Muntoni, Francesco
AU - Greenberg, Cheryl R.
AU - Gary, Françoise
AU - Urtizberea, Jon Andoni
AU - Duboc, Denis
AU - Fardeau, Michel
AU - Toniolo, Daniela
AU - Schwartz, Ketty
PY - 1999/3
Y1 - 1999/3
N2 - 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. 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. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form. 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. 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.
AB - 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. 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. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form. 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. 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.
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U2 - 10.1038/6799
DO - 10.1038/6799
M3 - Article
C2 - 10080180
AN - SCOPUS:0032977685
VL - 21
SP - 285
EP - 288
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 3
ER -