OMIA 002105-9940 : Neuroaxonal dystrophy, PLA2G6-related in Ovis aries

In other species: dog

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 256600 (trait) , 610217 (trait) , 612953 (trait) , 603604 (gene)

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]"

Breed: Swaledale.

Associated gene:

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

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
Swaledale Neuroaxonal dystrophy, PLA2G6-related PLA2G6 nonsense (stop-gain) 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
Swaledale Neuroaxonal dystrophy, PLA2G6-related PLA2G6 splicing 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

Reference


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.

Edit History


  • Created by Frank Nicholas on 11 Nov 2020
  • Changed by Frank Nicholas on 11 Nov 2020