OMIA 001594-9615 : Hyperekplexia (Startle disease) in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 149400

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Cross-species summary: Also known as startle disease

Inheritance: Gill et al. (2019): "a rapid genotyping test that revealed heterozygosity for the deletion in the dam and sire and three other siblings, confirming recessive inheritance."

Murphy et al. (2019): "Family members were genotyped for the deletion, and findings were consistent with an autosomal recessive inheritance pattern."

Molecular basis: Gill et al. (2011): "analysis of SLC6A5 revealed a homozygous 4.2 kb microdeletion encompassing exons 2 and 3 in both affected [Irish Wolfhound] animals.'

Murphy et al. (2019): "Whole genome resequencing of an affected [Spanish greyhound] dog revealed a homozygous two base pair deletion in the ninth exon of SLC6A5, encoding the presynaptic glycine transporter. The deletion is predicted to cause a frameshift, p.S460FfsX47, leading to a premature stop codon that truncates over a third of the protein."

Prevalence: Murphy et al. (2019): "The [Spanish Greyhound] pathogenic variant was absent from 34 unrelated greyhounds, 659 domestic dogs of pure and mixed breeds, and 54 wild canids, suggesting it occurred recently and may be private to the family."

Breeds: Irish Wolfhound, Spanish greyhound.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SLC6A5 solute carrier family 6 (neurotransmitter transporter), member 5 Canis lupus familiaris 21 NC_006603.3 (42581931..42639870) SLC6A5 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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
Irish Wolfhound Hyperekplexia (Startle disease) SLC6A5 deletion, gross (>20) "a homozygous 4.2kb microdeletion encompassing exons 2 and 3 " 2011 21420493
Spanish greyhound Hyperekplexia (Startle disease) SLC6A5 deletion, small (<=20) CanFam3.1 21 p.S460FfsX47 2019 30847549

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2019 Murphy, S.C., Recio, A., de la Fuente, C., Guo, L.T., Shelton, G.D., Clark, L.A. :
A glycine transporter SLC6A5 frameshift mutation causes startle disease in Spanish greyhounds. Hum Genet :, 2019. Pubmed reference: 30847549. DOI: 10.1007/s00439-019-01986-x.
2011 Gill, JL., Capper, D., Vanbellinghen, JF., Chung, SK., Higgins, RJ., Rees, MI., Shelton, GD., Harvey, RJ. :
Startle disease in Irish wolfhounds associated with a microdeletion in the glycine transporter GlyT2 gene. Neurobiol Dis 43:184-9, 2011. Pubmed reference: 21420493. DOI: 10.1016/j.nbd.2011.03.010.
1984 Fox, J.G., Averill, D.R., Hallett, M., Schunk, K. :
Familial reflex myoclonus in Labrador Retrievers. Am J Vet Res 45:2367-70, 1984. Pubmed reference: 6524730.

Edit History


  • Created by Frank Nicholas on 01 Aug 2011
  • Changed by Frank Nicholas on 10 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 22 May 2019