COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy

Barbara Gandolfi, Robert A Grahn, Erica K. Creighton, D. Colette Williams, Peter J Dickinson, Beverly Sturges, Ling T. Guo, G. Diane Shelton, Peter A J Leegwater, Maria Longeri, Richard Malik, Leslie A Lyons

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Some Devon Rex and Sphynx cats have a variably progressive myopathy characterized by appendicular and axial muscle weakness, megaesophagus, pharyngeal weakness and fatigability with exercise. Muscle biopsies from affected cats demonstrated variable pathological changes ranging from dystrophic features to minimal abnormalities. Affected cats have exacerbation of weakness following anticholinesterase dosing, a clue that there is an underlying congenital myasthenic syndrome (CMS). A genome-wide association study and whole-genome sequencing suggested a causal variant for this entity was a c.1190G>A variant causing a cysteine to tyrosine substitution (p.Cys397Tyr) within the C-terminal domain of collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). Alpha-dystroglycan expression, which is associated with COLQ anchorage at the motor end-plate, has been shown to be deficient in affected cats. Eighteen affected cats were identified by genotyping, including cats from the original clinical descriptions in 1993 and subsequent publications. Eight Devon Rex and one Sphynx not associated with the study were identified as carriers, suggesting an allele frequency of ~2.0% in Devon Rex. Over 350 tested cats from other breeds did not have the variant. Characteristic clinical features and variant presence in all affected cats suggest a model for COLQ CMS. The association between the COLQ variant and this CMS affords clinicians the opportunity to confirm diagnosis via genetic testing and permits owners and breeders to identify carriers in the population. Moreover, accurate diagnosis increases available therapeutic options for affected cats based on an understanding of the pathophysiology and experience from human CMS associated with COLQ variants.

Original languageEnglish (US)
Pages (from-to)711-715
Number of pages5
JournalAnimal Genetics
Volume46
Issue number6
DOIs
StatePublished - Dec 1 2015

Fingerprint

muscular diseases
Felidae
Muscular Diseases
Cats
cats
Congenital Myasthenic Syndromes
Dystroglycans
Motor Endplate
megaesophagus
muscles
Esophageal Achalasia
Genome-Wide Association Study
Cholinesterase Inhibitors
Muscle Weakness
Genetic Testing
Acetylcholinesterase
acetylcholinesterase
pathophysiology
Gene Frequency
genotyping

Keywords

  • collagen-like tail subunit of asymmetric acetylcholinesterase
  • congenital myasthenic syndrome
  • domestic cat
  • Felis catus silvestris

ASJC Scopus subject areas

  • Genetics
  • Animal Science and Zoology

Cite this

COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy. / Gandolfi, Barbara; Grahn, Robert A; Creighton, Erica K.; Williams, D. Colette; Dickinson, Peter J; Sturges, Beverly; Guo, Ling T.; Shelton, G. Diane; Leegwater, Peter A J; Longeri, Maria; Malik, Richard; Lyons, Leslie A.

In: Animal Genetics, Vol. 46, No. 6, 01.12.2015, p. 711-715.

Research output: Contribution to journalArticle

Gandolfi, B, Grahn, RA, Creighton, EK, Williams, DC, Dickinson, PJ, Sturges, B, Guo, LT, Shelton, GD, Leegwater, PAJ, Longeri, M, Malik, R & Lyons, LA 2015, 'COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy', Animal Genetics, vol. 46, no. 6, pp. 711-715. https://doi.org/10.1111/age.12350
Gandolfi, Barbara ; Grahn, Robert A ; Creighton, Erica K. ; Williams, D. Colette ; Dickinson, Peter J ; Sturges, Beverly ; Guo, Ling T. ; Shelton, G. Diane ; Leegwater, Peter A J ; Longeri, Maria ; Malik, Richard ; Lyons, Leslie A. / COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy. In: Animal Genetics. 2015 ; Vol. 46, No. 6. pp. 711-715.
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AU - Sturges, Beverly

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