title: Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing.
abstract: BACKGROUND
  The aim of this study is to describe a new mutation in the LMNA gene diagnosed by whole exome sequencing.
  
  
  METHODS
  A two-generation kindred with recessive limb-girdle muscular dystrophy was evaluated by exome sequencing of the proband's DNA.
  
  
  RESULTS
  Exome sequencing disclosed 194,618 variants (170,196 SNPs, 8482 MNPs, 7466 insertions, 8307 deletions, and 167 mixed combinations); 71,328 were homozygotic and 123,290 were heterozygotic, with 11,753 non-synonymous, stop-gain, stop-loss, or frameshift mutations occurring in the coding region or nearby intronic region. The cross-referencing of these mutations in candidate genes for muscular dystrophy showed a homozygote mutation c.G674A in exon 4 of LMNA causing a protein change R225Q in an arginine conserved from human to Xenopus tropicalis and in lamin B1.
  
  
  CONCLUSIONS
  This technique will be preferred for studying patients with muscular dystrophy in the coming years.
authors.affiliation: Servicio de Neurologia, Hospital Ramon y Cajal and Universidad de Alcala, 28034 Madrid, Spain. adriano.jimenez@hrc.es
authors.forename: Adriano
authors.initials: A
authors.lastname: Jimenez-Escrig
authors.forename: Isabel
authors.initials: I
authors.lastname: Gobernado
authors.forename: Mercedes
authors.initials: M
authors.lastname: Garcia-Villanueva
authors.forename: Antonio
authors.initials: A
authors.lastname: Sanchez-Herranz
mesh_terms: D017668:Age of Onset; D000818:Animals; D001706:Biopsy; D003402:Creatine Kinase / Q000097:blood; D004172:Diplopia / Q000209:etiology; D018450:Disease Progression; D059472:Exome / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014981:Xenopus / Q000235:genetics
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D003402:Creatine Kinase