title: Identification of new mutations in the Emery-Dreifuss muscular dystrophy gene and evidence for genetic heterogeneity of the disease.
abstract: The Emery-Dreifuss Muscular Dystrophy (EDMD) is an X-linked recessive muscular disorder characterized by early contractures of the elbows, Achilles tendons and postcervical muscles, slowly progressing muscle wasting and weakness and a cardiomyopathy characterized by conduction defects. Heart block is a frequent cause of death. Finding of mutations in one of the transcripts in the critical region in distal Xq28 led to the identification of the gene responsible for the disease. We now report the sequence of the gene which is 2100 bp long and the development of a set of primers to amplify and sequence the gene from patients' DNA. Eight unrelated X-linked familial cases were studied and they all carried different mutations, showing that lack of emerin in cardiac and skeletal muscle is the cause of the X-linked disease. No mutations were found in a family where the female carrier was affected nor in a sporadic case with a well established diagnosis of EDMD. Our findings suggest genetic heterogeneity of EDMD, and that at least two genes, the X-linked STA gene and one unidentified autosomal gene, are responsible for the disease.
authors.affiliation: Istituto di Genetica Biochimica ed Evoluzionistica CNR, Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bione
authors.forename: K
authors.initials: K
authors.lastname: Small
authors.forename: V M
authors.initials: VM
authors.lastname: Aksmanovic
authors.forename: M
authors.initials: M
authors.lastname: D'Urso
authors.forename: A
authors.initials: A
authors.lastname: Ciccodicola
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.forename: W
authors.initials: W
authors.lastname: Kress
authors.forename: J R
authors.initials: JR
authors.lastname: Yates
authors.forename: S T
authors.initials: ST
authors.lastname: Warren
mesh_terms: D001483:Base Sequence; D002423:Cause of Death; D002874:Chromosome Mapping; D017931:DNA Primers; D018076:DNA, Complementary; D005260:Female; D006580:Genetic Carrier Screening; D006327:Heart Block / Q000209:etiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D013946:Thymopoietins / Q000235:genetics*; D014960:X Chromosome
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin