In other species: dog

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 256600 (trait) , 610217 (trait) , 612953 (trait) , 603604 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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, United Kingdom of Great Britain and Northern Ireland (Sheep) (VBO_0015942).
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: