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

Gisèle Bonne, Marina Raffaele Di Barletta, Shaida Varnous, Henri Marc Bécane, El Hadi Hammouda, Luciano Merlini, Francesco Muntoni, Cheryl R. Greenberg, Françoise Gary, Jon Andoni Urtizberea, Denis Duboc, Michel Fardeau, Daniela Toniolo, Ketty Schwartz

Research output: Contribution to journalArticlepeer-review

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. 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.

Original languageEnglish
Pages (from-to)285-288
Number of pages4
JournalNature Genetics
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 1999

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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