OMIA:002105-9940 : Neuroaxonal dystrophy, PLA2G6-related in Ovis aries (sheep)
In other species: dog
Categories: Nervous system phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2020
Inheritance: Letko et al. (2020): "The sire of the five cases was heterozygous for the exon 8 variant, and all the dams of the five NAD-affected lambs were heterozygous for the intron 2 variant . . . . Interestingly, only the five affected animals carried both variants in a heterozygous state, which was consistent with a compound heterozygous inheritance . . . . From the 13 clinically normal lambs, three were homozygous wild type for both PLA2G6 variants, seven were heterozygous for the exon 8 variant and three were heterozygous for the intron 2 variant."
Molecular basis: Letko et al. (2020): "All [5 affected] cases were carriers of a compound heterozygous splice site variant in intron 2 and a nonsense variant in exon 8. Herein we present evidence for the occurrence of a familial novel form of recessively inherited NAD in sheep due to allelic heterogeneity at PLA2G6."
Clinical features: Letko et al. (2020): "Affected lambs showed progressive ataxia and stiff gait and subsequent histopathological analysis revealed the widespread presence of axonal spheroid indicating neuronal degeneration. Thus, the observed clinical phenotype could be explained by a novel form of NAD [Neuroaxonal dystrophy]"
Swaledale, United Kingdom of Great Britain and Northern Ireland (Sheep) (VBO_0015942).
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|
|PLA2G6||phospholipase A2 group VI||Ovis aries||3||NC_056056.1 (215782683..215721878)||PLA2G6||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|
|1267||Swaledale, United Kingdom of Great Britain and Northern Ireland (Sheep)||Neuroaxonal dystrophy, PLA2G6-related||PLA2G6||nonsense (stop-gain)||Naturally occurring variant||Oar_rambouillet_v1.0||3||g.230750869G>A||c.1186C>T||p.(Q396*)||Oar_rambouillet_v1.0: g.230750869G>A; XM_027968104.1 [shorter transcript] and XM_012175630.3 [longer transcript]: c.1186C>T; XP_027823905.1: p.Gln396* in the shorter transcript; XP_012031020.2: p.Leu396Phe in the longer transcript (Letko et al., 2020). Only the former variant peptide is tabulated here.||2021||33159255|
|1266||Swaledale, United Kingdom of Great Britain and Northern Ireland (Sheep)||Neuroaxonal dystrophy, PLA2G6-related||PLA2G6||splicing||Naturally occurring variant||Oar_rambouillet_v1.0||3||g.230766713T>C||c.336-2A>G||p.(L71Wfs*3)||Oar_rambouillet_v1.0: g.230766713T>C; XM_012175630.3: c.336-2A>G; XP_012031020.2: p.Leu71TrpfsTer3 (Letko et al., 2020)||2021||33159255|
Cite this entry
|2021||Letko, A., Strugnell, B., Häfliger, I.M., Paris, J.M., Waine, K., Drögemüller, C., Scholes, S. :|
|Compound heterozygous PLA2G6 loss-of-function variants in Swaledale sheep with neuroaxonal dystrophy. Mol Genet Genomics 296:235-42, 2021. Pubmed reference: 33159255 . DOI: 10.1007/s00438-020-01742-1.|
- Created by Frank Nicholas on 11 Nov 2020
- Changed by Frank Nicholas on 11 Nov 2020