Identification of a Novel Frameshift Mutation in the DMD Gene as the Cause of Muscular Dystrophy in a Norfolk Terrier Dog
C.A. Jenkins; O.P. Forman; C.S. Mellersh
Kennel Club Genetics Centre, Animal Health Trust, Lanwades Park, Newmarket, Suffolk, UK
Dystrophin-deficient muscular dystrophy (DD-MD) is an X-linked disease in humans (Duchenne muscular dystrophy, DMD) and dogs. In DD-MD the lack of functional dystrophin protein causes advancing muscle weakness, respiratory problems, and cardiomyopathy. This results in the loss of mobility and reduced life expectancy. Dystrophin-deficient muscular dystrophy is currently incurable, and the dog is an ideal model for the disease because the canine phenotype is very similar to that seen in humans. A six-month-old Norfolk terrier was referred to the Animal Health Trust neurology unit with suspected DD-MD, which was confirmed by clinical investigations and muscle biopsy results. Dystrophin-deficient muscular dystrophy had not been previously described in this breed. We carried out exon resequencing of the canine Duchenne muscular dystrophy (DMD) gene to screen for potential disease-causing mutations. The sequence data generated from all coding DMD exons revealed a 1-bp deletion in exon 22, causing a frameshift and premature termination of the coding sequence. Gene expression analysis (quantitative PCR) indicated reduced levels of dystrophin transcript in the DD-MD case and the absence of full-length dystrophin protein was confirmed by western blotting. The finding represents a novel mutation causing DD-MD in the dog.