OMIA:001594-9615 : Hyperekplexia (Startle disease), SLC6A5-related 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:
Single-gene trait/disorder: yes
Mode of inheritance: Autosomal recessive
Disease-related: yes
Key variant known: yes
Year key variant first reported: 2011
Cross-species summary:
Renamed from 'Hyperekplexia (Startle disease)' to 'Hyperekplexia (Startle disease), SLC6A5-related' [12/06/2024]
See also entries for 'OMIA:000689 : Hyperekplexia, GLRA1-related'
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
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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.
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.
2023 | Cocostîrc, V., Paștiu, A.I., Pusta, D.L. : |
An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568, 2023. Pubmed reference: 38003185. DOI: 10.3390/ani13223568. | |
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