title: Genomic duplication in Dyggve Melchior Clausen syndrome, a novel mutation mechanism in an autosomal recessive disorder.
abstract: BACKGROUND
  Dyggve Melchior Clausen syndrome (DMC) is a severe autosomal recessive skeletal dysplasia associated with mental retardation. Direct sequencing of genomic DNA has identified causative mutations in the gene Dymeclin (chromosome 18q12-21), with the majority predicting the generation of a truncated protein product.
  
  
  OBJECTIVE
  To carry out molecular genetic studies in three DMC kindreds.
  
  
  RESULTS
  Two novel nonsense mutations and two complex genomic duplication events resulting in exon repetition were identified.
  
  
  CONCLUSIONS
  Exon dosage assessment or mRNA analysis, in addition to direct genomic DNA sequencing, should be employed in the investigation of DMC affected individuals. Genomic duplication may be the causative mutation mechanism in other autosomal recessive disorders.
authors.affiliation: Division of Medical Genetics, Department of Genetics and Cardiovascular Science, University of Leicester, Leicester, UK.
authors.forename: E
authors.initials: E
authors.lastname: Kinning
authors.forename: C
authors.initials: C
authors.lastname: Tufarelli
authors.forename: W S
authors.initials: WS
authors.lastname: Winship
authors.forename: M A
authors.initials: MA
authors.lastname: Aldred
authors.forename: R C
authors.initials: RC
authors.lastname: Trembath
mesh_terms: D005192:Family Health; D005260:Female; D020440:Gene Duplication; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013577:Syndrome
chemical_list: C477370:DYM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger