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

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 604159 (gene) , 614618 (trait)

Links to relevant human diseases in MONDO:

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."

Clinical features: Clinical signs begin at birth. Puppies display an involuntary ‘startle response’ characterised by generalised or intermittent extensor rigidity induced by unexpected handling or noise (Gill et al., 2011). Neonatal Irish wolfhounds have been reported to develop cyanosis and pneumonia when feeding due to extended periods of rigidity causing apnoea (Gill et al., 2011). Neonatal Spanish greyhounds were unable to properly walk or stand due to episodes of extensor rigidity. When owners attempted to assists the puppies with walking, their touch induced further extensor rigidity (Murphy et al. ̧ 2019). Neonatal death in hyperekplexic puppies is not uncommon due to the complications of feeding and breathing during hypertonic episodes/startle responses. IT thanks DVM student Emily Ketchum, who provided the basis of this contribution in May 2023.

Pathology: Post-mortem examination of Irish Wolfhound puppies with hyperekplexia have revealed no obvious muscular or neurological lesions resulting from the generic variants (Gill et al., 2011). IT thanks DVM student Emily Ketchum, who provided the basis of this contribution in May 2023.

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 (Dog) (VBO_0200706), Spanish Greyhound (Dog) (VBO_0201274).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

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_051825.1 (43704400..43760475) 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.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
638 Irish Wolfhound (Dog) Hyperekplexia (Startle disease) SLC6A5 deletion, gross (>20) Naturally occurring variant CanFam3.1 21 g.42583699_42587925del c.-52_562+504del XM_005633757.1; "a homozygous 4.2kb [4227bp] microdeletion encompassing exons 2 and 3" 2011 21420493
1080 Spanish Greyhound (Dog) Hyperekplexia (Startle disease) SLC6A5 deletion, small (<=20) Naturally occurring variant CanFam3.1 21 g.42612546_42612547del c.1379_1380delCT p.(S460Ffs*47) XM_022407940.1; XP_022263648.1 2019 30847549 Genomic coordinates in CanFam3.1 provided by Robert Kuhn.

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001594-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2021 Cerda-Gonzalez, S., Packer, R.A., Garosi, L., Lowrie, M., Mandigers, P.J.J., O'Brien, D.P., Volk, H.A. :
International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230, 2021. Pubmed reference: 33769611. DOI: 10.1111/jvim.16108.
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 138:509-513, 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
  • Changed by Imke Tammen2 on 02 Nov 2021
  • Changed by Imke Tammen2 on 07 May 2023