PMID:10080180

Citation	Bonne, G, Di Barletta, MR, Varnous, S, Bécane, HM, Hammouda, EH, Merlini, L, Muntoni, F, Greenberg, CR, Gary, F, Urtizberea, JA, Duboc, D, Fardeau, M, Toniolo, D and Schwartz, K (1999) Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat. Genet. 21:285-8
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.
Links	PubMed Online version:10.1038/6799
Keywords	Amino Acid Sequence; Cloning, Molecular; Deoxyribonuclease HpaII/genetics; Deoxyribonucleases, Type II Site-Specific/genetics; Exons; Female; Genes, Dominant; Haplotypes; Humans; Immunohistochemistry; Lamin Type A; Lamins; Male; Microsatellite Repeats; Molecular Sequence Data; Muscular Dystrophies/genetics; Muscular Dystrophy, Emery-Dreifuss; Mutation; Myocardium/metabolism; Myocardium/pathology; Nuclear Proteins/analysis; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Pedigree; Sequence Analysis, DNA; Sequence Homology, Amino Acid
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:LMNA	part_of	GO:0048471: perinuclear region of cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:LMNA	involved_in	GO:0007517: muscle organ development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:LMNA	part_of	GO:0005638: lamin filament	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete

References

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