In other species: sheep

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: 2017

Species-specific description: Neuroaxonal dystrophy in Papillon dogs was fist reported in 1995 in England [Franklin et al., 19851], and has since been reported in several other countries. Tsuboi et al. (2017) identified the likely causal variant.

Molecular basis: Tsuboi et al. (2017): PLA2G6 c.1579G>A; p.T526A

Clinical features: Tsuboi et al. (2017) investigated three affected Papillon dogs: "The affected dogs initially developed intention tremor and hypermetria at a very young age, and the symptoms gradually progressed to cerebellar ataxia, tetraplegia, blindness, and deafness." Onset of disease was between 13-16 weeks of age and death occurred between 7 to 8 month of age.

Pathology: Tsuboi et al. (2017) investigated three affected Papillon dogs: "Histopathologically, multiple spheroid formation is observed throughout the central nervous system, including the cerebrum, hippocampus, thalamus, mesencephalon, cerebellum, pons, medulla oblongata, and dorsal horn of the spinal cord, while the peripheral nerves are generally unaffected."

Prevalence: Raj and Giger (2020): "Archived samples from Papillons clinically diagnosed with NAD prior to 2015 as well as samples obtained from 660 Papillons from North America and Europe between 2015 and 2017 were screened for the presence of this PLA2G6 gene variant (XM_022424454.1:c.1579G > A) ... .17.5% of the 660 tested Papillons were heterozygotes, resulting in a variant allele frequency of 0.092 in this initial survey. Since then, screening for NAD in Papillons by at least 10 other laboratories and data from the Health Committee of Papillon Club of America gathered between 2017 and 2019 reveal a variant allele frequency of 0.047."

Breed: Papillon (Dog) (VBO_0200985).
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: