Dog (Canis lupus familiaris) — X-linked muscular dystrophy; Dystrophin-deficient muscular dystrophy (hereditary; OMIA-verified species predisposition)

Dog (Canis lupus familiaris) — X-linked muscular dystrophy; Dystrophin-deficient muscular dystrophy (hereditary; OMIA-verified species predisposition)

Source: first-hand OMIA (University of Sydney) species-specific hereditary-disorder record, saved verbatim to source_file; every claim below is a C1 byte-substring of it.

Claims

• Species: Dog (Canis lupus familiaris)
• Disorder: X-linked muscular dystrophy; Dystrophin-deficient muscular dystrophy
• Mode of inheritance: Carrier females usually do not show clinical signs. However, due to random X inactivation, they can occasionally present with limb weakness and highly elevated serum creatine kinase, or show changes on electromyography or biopsy (Shelton et al., 2004; Kornegay et al., 2011).
• Summary: Also known as Golden Retriever Muscular Dystrophy (GRMD), because this is the breed in which this disorder was first documented. This is the canine homologue of human Duchenne muscular dystrophy, which is caused by mutations in the dystrophin gene and is characterized by progressive weakness and muscle wasting that is ultimately fatal. Clinical signs begin at 8-10 weeks of age. Absence of the dystrophin protein causes sarcolemma dysfunction, muscular hypercontraction, and ultimately, muscle fiber degeneration. The mode of inheritance is X-linked recessive. Edited by Meg Sleeper, VMD and Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT. All known canine DMD variants that cause Duchenne or Becker like muscular dystrophy are listed in this entry. This phene includes references to studies involving genetically modified organisms (GMO).
• Clin feat: Affected dogs develop clinical signs at 8 to 10 weeks of age. Signs include a shuffling gait or shortened stride (“bunny hopping”), inability to completely open the jaw, difficulty eating, thickening of the base of the tongue, excessive salivation, abduction of front paws, adduction of stifles and hocks, and prominent wasting of temporal and trunk muscles (Shelton, 2004; Valentine et al., 1992; Kornegay et al., 2011). Other signs include spinal and costal curvature, resulting in a crouched posture (Valentine et al., 1992). Elevated serum creatine kinase concentrations (up to 300 times greater than normal) begins during the first week of life age, and is exacerbated by exercise (Valentine et al., 1992). In breeds where a mutation has not been reported, affected dogs can be tentatively diagnosed by immunohistochemical tests for the presence or absence of dystrophin protein in skeletal muscle biopsy (Shelton and Engvall 2002).
• Pathology: Clinical signs are caused by the absence of dystrophin protein. Affected animals initially have sarcolemma dysfunction, which results in an increased intracellular calcium and muscle fiber hypercontraction. These are followed by muscle fiber degeneration and necrosis, with some regeneration (Howell et al., 1997). Eventually, muscle fibrosis, mineralization and fat infiltration occur in both skeletal and cardiac muscle. Lesions in cardiac muscle, which are analogous but can be less severe, are usually in the ventricles, and usually occur after 6 months of age (Howell et al., 1997).
• Control: Female relatives of affected dogs should be tested to identify carriers. Breeding of affected or carrier animals should be avoided.

Associated gene(s)

Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.

• Gene: Entrez Gene ID 606758 (no symbol in OMIA GeneSynonym) — OMIA Phene_Gene
• OMIA molecular-genetics note: All causative mutations occur within the dystrophin gene, although the molecular basis of the dystrophin mutation may be different between breeds. <br>In the Golden Retriever, there is a point mutation in the consensus splice acceptor site in exon 6 of the dystrophin gene (omia.variant:366), such that exon 7 is skipped during mRNA processing. The amino acid frame shift causes premature termination…

Evidence (references)

Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.

• 1988. The homologue of the Duchenne locus is defective in X-linked muscular dystrophy of dogs. Nature — PubMed:PMID3290691 | DOI:10.1038/334154a0 — OMIA Phene_Article / Article
• 1988. Canine X-Linked Muscular Dystrophy - An Animal Model of Duchenne Muscular Dystrophy - Clinical Studies. Journal of the Neurological Sciences — PubMed:PMID3225630 — OMIA Phene_Article / Article
• 1990. Canine X-Linked Muscular Dystrophy - Morphologic Lesions. Journal of the Neurological Sciences — PubMed:PMID2370557 — OMIA Phene_Article / Article
• 1992. An Error in Dystrophin Messenger RNA Processing in Golden Retriever Muscular Dystrophy, an Animal Homologue of Duchenne Muscular Dystrophy. Genomics — PubMed:PMID1577476 — OMIA Phene_Article / Article
• 1992. Canine X-Linked Muscular Dystrophy as an Animal Model of Duchenne Muscular Dystrophy - A Review. American Journal of Medical Genetics — PubMed:PMID1536178 | DOI:10.1002/ajmg.1320420320 — OMIA Phene_Article / Article
• 1992. The xmd Dog - Molecular and Phenotypic Characteristics. Duchenne Muscular Dystrophy — OMIA Phene_Article / Article
• 1992. Exon Skipping During Dystrophin Messenger RNA Processing in the Canine Homologue of Duchenne Muscular Dystrophy. Duchenne Muscular Dystrophy — OMIA Phene_Article / Article
• 1992. Potential Strategies for Gene Therapy in Golden Retriever Muscular Dystrophy. Duchenne Muscular Dystrophy — OMIA Phene_Article / Article
• 1993. Canine X-Linked Muscular Dystrophy in Belgian Groenendaeler Shepherds. Journal of the American Animal Hospital Association — OMIA Phene_Article / Article
• 1995. Canine X-linked muscular dystrophy in Belgian Groenendaeler shepherds. Vlaams Diergeneeskundig Tijdschrift — OMIA Phene_Article / Article
• 1995. Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs. Journal of Clinical Investigation — PubMed:PMID7560097 | DOI:10.1172/JCI118251 — OMIA Phene_Article / Article
• 1995. Congenital dystrophy-like myopathy in a brittany spaniel puppy. Progress in Veterinary Neurology — OMIA Phene_Article / Article
• (195 additional references in OMIA)

Comparative medicine (human OMIM)

Derived from OMIA database dump (omia.xml, local); structured field, not verbatim prose. First-hand values below are verbatim substrings of the topic's pdf-raw/omia/<phene_id>.txt source file.

• OMIM:310200 (type: trait) — OMIA Group_OMIM (via OMIA_ID)
• OMIM:300377 (type: gene) — OMIA Group_OMIM (via OMIA_ID)