A COLQ Missense Mutation in Sphynx and Devon Rex Cats with Congenital Myasthenic Syndrome

PLoS One. 2015 Sep 1;10(9):e0137019. doi: 10.1371/journal.pone.0137019. eCollection 2015.


An autosomal recessive neuromuscular disorder characterized by skeletal muscle weakness, fatigability and variable electromyographic or muscular histopathological features has been described in the two related Sphynx and Devon Rex cat breeds (Felis catus). Collection of data from two affected Sphynx cats and their relatives pointed out a single disease candidate region on feline chromosome C2, identified following a genome-wide SNP-based homozygosity mapping strategy. In that region, we further identified COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase) as a good candidate gene, since COLQ mutations were identified in affected humans and dogs with endplate acetylcholinesterase deficiency leading to a synaptic form of congenital myasthenic syndrome (CMS). A homozygous c.1190G>A missense variant located in exon 15 of COLQ, leading to a C397Y substitution, was identified in the two affected cats. C397 is a highly-conserved residue from the C-terminal domain of the protein; its mutation was previously shown to produce CMS in humans, and here we confirmed in an affected Sphynx cat that it induces a loss of acetylcholinesterase clustering at the neuromuscular junction. Segregation of the c.1190G>A variant was 100% consistent with the autosomal recessive mode of inheritance of the disorder in our cat pedigree; in addition, an affected, unrelated Devon Rex cat recruited thereafter was also homozygous for the variant. Genotyping of a panel of 333 cats from 14 breeds failed to identify a single carrier in non-Sphynx and non-Devon Rex cats. Finally, the percentage of healthy carriers in a European subpanel of 81 genotyped Sphynx cats was estimated to be low (3.7%) and 14 control Devon Rex cats were genotyped as wild-type individuals. Altogether, these results strongly support that the neuromuscular disorder reported in Sphynx and Devon Rex breeds is a CMS caused by a unique c.1190G>A missense mutation, presumably transmitted through a founder effect, which strictly and slightly disseminated in these two breeds. The presently available DNA test will help owners avoid matings at risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics*
  • Animals
  • Cats
  • Molecular Sequence Data
  • Muscle Proteins / genetics*
  • Mutation, Missense*
  • Myasthenic Syndromes, Congenital / genetics*
  • Species Specificity


  • Muscle Proteins
  • Acetylcholinesterase

Associated data

  • GENBANK/KR049220
  • GENBANK/KR049221
  • GENBANK/KT223392
  • GENBANK/KT223393

Grants and funding

This work was specifically supported by the LOOF (Livre Officiel des Origines Félines, www.loof.asso.fr). Purchase of the Illumina Infinium Feline 63K iSelect DNA array was allowed thanks to the Morris Animal Foundation (Grant-In-Aid Agreement n°D14FE-563). Support for the development of the Illumina Infinium Feline 63K iSelect DNA array was provided by the Morris Animal Foundation (www.morrisanimalfoundation.org) via a donation from Hill’s Pet Food, Inc. Medical genetics tools were partly provided by the CNM Project (www.labradorcnm.com). These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Antagene provided support in the form of salary for author [AT] and research materials (DNA collection), but had no additional role in the study design, data analysis, decision to publish, or preparation of the manuscript.