OMIA:000689-9615 : Hyperekplexia, GLRA1-related in Canis lupus familiaris (dog)

In other species: horse , taurine cattle

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 149400 (trait) , 138491 (gene)

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: 2023

Cross-species summary: Renamed from 'myoclonus' to 'hyperekplexia, GLRA1-related' [27/5/2023]
See also entries for 'OMIA:001594 : Hyperekplexia (Startle disease), SLC6A5-related'

Molecular basis: Heinonen et al. (2023): "Whole genome sequence data analysis of two affected dogs revealed a 36-bp deletion spanning the exon–intron boundary in the glycine receptor alpha 1 (GLRA1) gene. Further validation in pedigree samples and an additional cohort of 127 Miniature Australian Shepherds, 45 Miniature American Shepherds and 74 Australian Shepherds demonstrated complete segregation of the variant with the disease, according to an autosomal recessive inheritance pattern."

Clinical features: Heinonen et al. (2023) report Miniature Australian Shepherd dogs with "episodes of muscle stiffness that could occasionally be triggered by acoustic stimuli."

Pathology: Heinonen et al. (2023): "Morphological examination of the left semitendinosus and cranial tibial muscles revealed a moderate to marked increase of interfibrillar and subsarcolemmal lipid droplets going together with subhistological mitochondrial crowding and occasional cristae abnormalities ... . Individual fibers at ultrastructural level also revealed I-band misalignment and early necrotic changes. There was no evidence of myonuclear abnormalities, fiber mineralization, sarcoplasmic vacuolation, protein inclusions, or pathological storage of polysaccharides."

Breed: Miniature Australian Shepherd Dog (Dog) (VBO_0200881).
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
GLRA1 glycine receptor, alpha 1 Canis lupus familiaris 4 NC_051808.1 (57919593..57971180) GLRA1 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
1571 Miniature Australian Shepherd Dog (Dog) Hyperekplexia GLRA1 deletion, gross (>20) Naturally occurring variant UU_Cfam_GSD_1.0 4 g.58338954_58338989del published as a 36-bp deletion encompassing part of the intron 1 and exon 2 (chr4:g.58,338,953); coordinates in the this table are in accordance with HGVS nomenclature 2023 37222814

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000689-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

Reference

2023 Heinonen, T., Flegel, T., Müller, H., Kehl, A., Hundi, S., Matiasek, K., Fischer, A., Donner, J., Forman, O.P., Lohi, H., Hytönen, M.K. :
A loss-of-function variant in canine GLRA1 associates with a neurological disorder resembling human hyperekplexia. Hum Genet , 2023. Pubmed reference: 37222814. DOI: 10.1007/s00439-023-02571-z.

Edit History


  • Created by Imke Tammen2 on 27 May 2023
  • Changed by Imke Tammen2 on 27 May 2023