title: Novel and recurrent EMD mutations in patients with Emery-Dreifuss muscular dystrophy, identify exon 2 as a mutation hot spot.
abstract: Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder exhibiting a cardiomyopathy with cardiac conduction defects. X-linked EDMD arises from mutations in the EMD gene, which encodes for a nuclear membrane protein termed emerin. In this study, we describe novel and recurrent EMD mutations identified in 18 probands and three carriers from a cohort of 255 North American patients referred for EDMD genetic mutation analysis. Eight of these mutations are novel including six frameshift mutations (p.D9GfsX24, p.F39SfsX17, p.R45KfsX16, p.F190YfsX19, p.R203PfsX34 and p.R204PfsX7) and two non-sense mutations (p.S143X, p.W200X). Our data augment the number of EMD mutations by 13.8%, equating to an increase of 5.2% in the total known EMD mutations and to an increase of 6.0% in the number of different mutations. Analysis of the exon distribution of mutations within the EMD gene, suggests a nonrandom distribution, with exon 2 as a hot spot. This phenomenon may be due to its high GC content, which at 60% is the most GC-rich exon in the EMD gene.
authors.affiliation: Diagnostics Systems, BD Diagnostics, Durham, NC, USA.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Brown
authors.forename: Juergen
authors.initials: J
authors.lastname: Scharner
authors.forename: Kevin
authors.initials: K
authors.lastname: Felice
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Meriggioli
authors.forename: Mark
authors.initials: M
authors.lastname: Tarnopolsky
authors.forename: Matthew
authors.initials: M
authors.lastname: Bower
authors.forename: Peter S
authors.initials: PS
authors.lastname: Zammit
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Ellis
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D008565:Membrane Proteins; D009687:Nuclear Proteins; C092710:emerin