Genomic duplication in Dyggve Melchior Clausen syndrome, a novel mutation mechanism in an autosomal recessive disorder

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 t...

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Bibliographic Details
Published in:Journal of medical genetics 2005-12, Vol.42 (12), p.e70-e70
Main Authors: Kinning, E, Tufarelli, C, Winship, W S, Aldred, M A, Trembath, R C
Format: Article
Language:English
Subjects:
autosomal recessive
Deoxyribonucleic acid
Disease
DMC
DNA
dosage quotient
Dyggve Melchior Clausen syndrome
exon duplication
Family Health
Female
Gene Duplication
Genes
Genes, Recessive
Genetic Predisposition to Disease
Genomes
Genomics
Genotype & phenotype
Humans
Male
Models, Genetic
Muscular dystrophy
Mutation
Online Mutation Report
Osteochondrodysplasias - genetics
Pedigree
Proteins
Proteins - genetics
RNA, Messenger - metabolism
simple tandem repeat
skeletal dysplasia
STR
Studies
Syndrome
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Summary: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.
ISSN:0022-2593
1468-6244
1468-6244
DOI:10.1136/jmg.2005.033829