Initial survey of PLA2G6 missense variant causing neuroaxonal dystrophy in Papillon dogs in North America and Europe

BACKGROUND: An autosomal recessive, rapidly progressive degenerative neuropathy known as infantile neuroaxonal dystrophy (NAD) was originally reported in Papillion puppies in 1995. In 2015, a causative missense variant in the PLA2G6 gene was identified in three affected puppies. 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) using a TaqMan assay. RESULTS: Archived samples from affected puppies diagnosed prior to 2015 and three more recently acquired samples from Papillons clinically affected with NAD were all homozygous for the variant. SIFT analysis predicts that the PLA2G6 missense substitution (XP_022280162.1:p.Ala527Thr) will not be tolerated in the iPLA(2)β protein. Notably, 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. CONCLUSIONS: This survey and data from other laboratories documents the widespread presence of the PLA2G6 variant in the Papillon population in North America and Europe. Despite the apparent declining prevalence of the PLA2G6 variant, screening of Papillons intended for breeding is still recommended to avoid inadvertent production of puppies with infantile NAD.