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.
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: J M Friedman; Agnes Baross; Allen D Delaney; Adrian Ally; Laura Arbour; Linlea Armstrong; Jennifer Asano; Dione K Bailey; Sarah Barber; Patricia Birch; Mabel Brown-John; Manqiu Cao; Susanna Chan; David L Charest; Noushin Farnoud; Nicole Fernandes; Stephane Flibotte; Anne Go; William T Gibson; Robert A Holt; Steven J M Jones; Giulia C Kennedy; Martin Krzywinski; Sylvie Langlois; Haiyan I Li; Barbara C McGillivray; Tarun Nayar; Trevor J Pugh; Evica Rajcan-Separovic; Jacqueline E Schein; Angelique Schnerch; Asim Siddiqui; Margot I Van Allen; Gary Wilson; Siu-Li Yong; Farah Zahir; Patrice Eydoux; Marco A Marra Journal: Am J Hum Genet Date: 2006-07-25 Impact factor: 11.025
Authors: Jm Friedman; Shelin Adam; Laura Arbour; Linlea Armstrong; Agnes Baross; Patricia Birch; Cornelius Boerkoel; Susanna Chan; David Chai; Allen D Delaney; Stephane Flibotte; William T Gibson; Sylvie Langlois; Emmanuelle Lemyre; H Irene Li; Patrick MacLeod; Joan Mathers; Jacques L Michaud; Barbara C McGillivray; Millan S Patel; Hong Qian; Guy A Rouleau; Margot I Van Allen; Siu-Li Yong; Farah R Zahir; Patrice Eydoux; Marco A Marra Journal: BMC Genomics Date: 2009-11-16 Impact factor: 3.969
Authors: Daniel L Polla; Maria T O Cardoso; Mayara C B Silva; Isabela C C Cardoso; Cristina T N Medina; Rosenelle Araujo; Camila C Fernandes; Alessandra M M Reis; Rosangela V de Andrade; Rinaldo W Pereira; Robert Pogue Journal: PLoS One Date: 2015-09-18 Impact factor: 3.240