Initial survey of PLA2G6 missense variant causing neuroaxonal dystrophy in Papillon dogs in North America and Europe
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(2020) 7:17
RESEARCH
Canine Medicine and Genetics
Open Access
Initial survey of PLA2G6 missense variant causing neuroaxonal dystrophy in Papillon dogs in North America and Europe Karthik Raj and Urs Giger*
Abstract 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 iPLA2β 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. Keywords: Canine, Mutations, Screening, Breeding, Ataxia
Plain English summary Infantile neuroaxonal dystrophy (NAD) is a rare rapidly progressive disease first reported in Papillion dogs in 1995. Clinical manifestations of ataxia, head tremor, difficulty rising, discordant gate, limb extension, paresis, inability to prehend food and water, and blindness are observed by 1–3 months of age. A specific genetic variant in PLA2G6 was recently identified in three Papillons with NAD in Japan. We screened Papillons with a * Correspondence: [email protected] Section of Medical Genetics (PennGen Laboratories), School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey St., Philadelphia, PA 19104-6010, USA
clinical diagnosis of NAD received prior to 2015 and samples from an additional 660 Papillons from North America and Europe received between 2015 and 2017 for the presence of this gene variant. All samples from Papillons clinically affected with NAD were homozygous for the variant. Furthermore, 17.5% of all Papillons tested were asymptomatic heterozygotes, and therefore able to pass on the variant to their offspring. Since 2017, an increasing number of laboratories offer NAD screening of Papillons, often together
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