Genomic duplication in Dyggve Melchior Clausen syndrome, a novel mutation mechanism in an autosomal recessive disorder. Issue 12 (2nd December 2005)

• Record Type: Journal Article
• Authors: Kinning, E; Tufarelli, C; Winship, W S; Aldred, M A; Trembath, R C
• Is Part Of: Journal of medical genetics. Volume 42:Issue 12(2005)
• Page Start: e70
• Page End: e70
• Publication Date: 2005-12-02
• Subjects: DMC, Dyggve Melchior Clausen syndrome -- DQ, dosage quotient -- STR, simple tandem repeat; skeletal dysplasia -- Dyggve Melchior Clausen syndrome -- autosomal recessive -- exon duplication; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2005.033829
• Languages: English
• ISSNs: 1468-6244

Abstract

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.