OMIA:000689-9615 : Hyperekplexia, GLRA1-related in Canis lupus familiaris (dog)
Categories: Nervous system phene
Links to MONDO diseases:
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]
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."
Miniature Australian shepherd.
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|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|
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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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1571||Miniature Australian shepherd||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
|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.|
- Created by Imke Tammen2 on 27 May 2023
- Changed by Imke Tammen2 on 27 May 2023