title: Clinical variability and molecular diagnosis in a four-generation family with X-linked Emery-Dreifuss muscular dystrophy.
abstract: OBJECTIVE
  To describe the clinical variability of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) with cardiac involvement in a four-generation family with a novel mutation in the STA gene.
  
  
  METHODS
  Clinical data were provided for 4 affected males and a female carrier. The Western blot analysis of emerin was performed on lymphoblastoid cell lines and followed by sequencing of the emerin gene.
  
  
  RESULTS
  A thymine insertion at nucleotide 417 in exon 2, resulting in a frameshift with a premature stop codon at position 62 and absence of functional protein, was found in one of the three available patients. In ten-year-old proband's dizygotic twin-nephews the intermittent first-degree A-V block, atrial and ventricular ectopy, atrial runs, and exit sinus block were found, although the echocardiographic findings were normal. One of the twins also had short episodes of atrial fibrillation, idioventricular rhythm, and junctional rhythm.
  
  
  CONCLUSIONS
  Cardiac abnormalities in the proband's ten-year-old dizygotic twins without evident clinical features suggestive of EDMD were remarkable in contrast to the oldest patient in the family, who lived to the age of 63 without a pacemaker, and to the proband who had a very early onset of muscle wasting and weakness, and a pacemaker implantation at the age of 27. This striking intra-familial variability in cardiac involvement associated with specific null mutation (417 ins T) has practical early diagnostic and possibly preventive implications. It also points at genetic and environmental factors as causes of clinical features in X-EDMD.
authors.affiliation: Division of Neurogenetics, Department of Neurology, Zagreb University School of Medicine and Hospital Center, Kispaticeva 12, 10000 Zagreb, Croatia. nina.canki-klain@zg.tel.hr
authors.forename: N
authors.initials: N
authors.lastname: Canki-Klain
authors.forename: D
authors.initials: D
authors.lastname: Récan
authors.forename: D
authors.initials: D
authors.lastname: Milicić
authors.forename: S
authors.initials: S
authors.lastname: Llense
authors.forename: F
authors.initials: F
authors.lastname: Leturcq
authors.forename: N
authors.initials: N
authors.lastname: Deburgrave
authors.forename: J C
authors.initials: JC
authors.lastname: Kaplan
authors.forename: M
authors.initials: M
authors.lastname: Debevec
authors.forename: N
authors.initials: N
authors.lastname: Zurak
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002353:Carrier State; D003062:Codon; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D010641:Phenotype; D013946:Thymopoietins / Q000235:genetics
chemical_list: D003062:Codon; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin