OMIA 001928-9615 : Myasthenic syndrome, congenital, COLQ-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 603034

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Species-specific name: Congenital myasthenic syndromes

Species-specific symbol: CMS

Mapping: Having access to only two affected members of a single family, Rinz et al. (2014) were not able to conduct a GWAS to map this disorder. Instead they examined haplotype inheritance in the region of 18 comparative candidate genes (based on genes with known causal mutations for various types of CMS in humans), using relevant SNPs from the 173,662 SNPs in the Illumina CanineHD Infinium BeadChip, in the two affected littermates, five normal littermates and the two normal (but related) parents. Only one candidate gene (COLQ; officially known as LOC608697) [on chromosome CFA23] showed concordant inheritance.

Molecular basis: Subsequent sequencing by Rinz et al. (2014) of the primary candidate gene (COLQ or LOC608697; see Mapping section above) revealed a causal mutation as "a variant in exon 14 (c.1010T>C) that results in the substitution of a conserved amino acid (I337T) within the C-terminal domain. Both affected puppies were homozygous for this variant, and 16 relatives were heterozygous, while 288 unrelated Labrador Retrievers and 112 dogs of other breeds were wild-type."

Clinical features: As reported by Rinz et al. (2014): "Neurological examination was consistent with a generalized neuromuscular disease with marked short-strided tetraparesis that worsened with exercise. Postural reactions were preserved with the exception of hopping which was diminished in all limbs when the puppies were made to bear full weight. Spinal reflexes including the patellar, cranial tibial, and flexor withdrawals were reduced in all limbs. A pyridostigmine bromide challenge resulted in worsening of muscle weakness."

Breed: Labrador Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
LOC608697 2-hydroxyacyl-CoA lyase 1 Canis lupus familiaris 23 NC_006605.3 (27069676..27188247) LOC608697 Homologene, Ensembl, NCBI gene

Variants

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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Labrador Retriever Myasthenic syndrome, congenital LOC608697 missense c.1010T>C p.I337T 2014 25166616

Reference


2014 Rinz, C.J., Levine, J., Minor, K.M., Humphries, H.D., Lara, R., Starr-Moss, A.N., Guo, L.T., Williams, D.C., Shelton, G.D., Clark, L.A. :
A COLQ missense mutation in Labrador Retrievers having congenital myasthenic syndrome. PLoS One 9:e106425, 2014. Pubmed reference: 25166616. DOI: 10.1371/journal.pone.0106425.

Edit History


  • Created by Frank Nicholas on 06 Sep 2014
  • Changed by Frank Nicholas on 06 Sep 2014
  • Changed by Frank Nicholas on 09 Nov 2016