title: Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain of the lamin A/C gene.
abstract: BACKGROUND
  Autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) is a disorder characterized clinically by humeropelvic weakness, contractures, and cardiomyopathy, and genetically by mutations in the lamin A/C gene on 1q21.2-q21.3. Of the 14 lamin A/C gene mutations reported thus far, the four involving the rod domain have been associated with isolated cardiomyopathy and conduction-system disease. This is the first report of rod domain mutations in patients with the full EDMD-AD phenotype.
  
  
  METHODS
  Clinical, pathologic, and genetic data are provided on two families with EDMD-AD.
  
  
  RESULTS
  In both families, the full clinical spectrum of EDMD-AD was demonstrated. For the proband in family 1, sequence analysis detected a mutation within exon 2 of the lamin A/C gene. The missense mutation was due to a A448C base substitution causing a Thr150Pro amino acid change. For the proband of family 2, sequence analysis detected an in-frame 3-bp deletion (AAG 778-780 or 781-783) removing one of two adjacent lysine residues (K 260 or 261) of exon 4. Both mutations were in the central rod domain of the lamin A/C gene.
  
  
  CONCLUSIONS
  Mutations in the rod domain of the lamin A/C gene may cause the full clinical spectrum of EDMD-AD.
authors.affiliation: Department of Neurology, Division of Human Genetics, University of Connecticut School of Medicine, Farmington, USA. felice.nso.uchc.edu
authors.forename: K J
authors.initials: KJ
authors.lastname: Felice
authors.forename: R C
authors.initials: RC
authors.lastname: Schwartz
authors.forename: C A
authors.initials: CA
authors.lastname: Brown
authors.forename: C R
authors.initials: CR
authors.lastname: Leicher
authors.forename: M L
authors.initials: ML
authors.lastname: Grunnet
mesh_terms: D000293:Adolescent; D000328:Adult; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002878:Chromosomes, Human, Pair 1; D005091:Exons; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree
chemical_list: D007797:Laminin; C084098:laminin A