Screening and Carrier Rate of Neuronal Ceroid Lipofuscinosis in Chihuahua Dogs in Japan

Abstract

Neuronal ceroid lipofuscinosis (NCL) is a group of rare lethal neurodegenerative lysosomal storage diseases that occur in a range of dog breeds, including Chihuahuas. Recently, a homozygous single base-pair deletion (c.846delT), which causes a frame shift generating a premature stop codon (p.Phe282Leufs13*) in the canine CLN7/MFSD8 gene, has been identified as a causative mutation for NCL in Chihuahuas. The objective of this study was to determine the frequency of the mutant allele and/or carrier rate of NCL in Chihuahuas in Japan using a newly designed real-time PCR assay. Samples of saliva were randomly collected from 1007 Chihuahua puppies during physical examinations prior to the transportation to pet shops. Screening results revealed a carrier rate of 1.29%, indicating a mutant allele frequency (0.00645) that is considered sufficiently high to warrant measures for the control and prevention of this lethal disease. The genotyping assay designed in this study could make a valuable contribution to the control and prevention of NCL.

Molecular Epidemiological Survey for Degenerative Myelopathy in German Shepherd Dogs in Japan: Allele Frequency and Clinical Progression Rate

“…In Japan, molecular epidemiological surveys have been carried out for several inherited canine diseases to determine the associated mutant allele frequencies and thereby evaluate the necessity of prevention measures [27][28][29][30][31]. Among these, lethal diseases characterized by progressive neurological dysfunction include GM1 gangliosidosis in Shiba Inus (mutant allele frequency = 0.00509) [27] and Mame Shibas (0.00246) [28], neuronal ceroid lipofuscinosis (NCL) in Chihuahuas (0.00645) [30], Sandhoff disease in Toy Poodles (0.00101) [29], and NCL in Border Collies (0.0405) [31].…”

“…In Japan, molecular epidemiological surveys have been carried out for several inherited canine diseases to determine the associated mutant allele frequencies and thereby evaluate the necessity of prevention measures [27][28][29][30][31]. Among these, lethal diseases characterized by progressive neurological dysfunction include GM1 gangliosidosis in Shiba Inus (mutant allele frequency = 0.00509) [27] and Mame Shibas (0.00246) [28], neuronal ceroid lipofuscinosis (NCL) in Chihuahuas (0.00645) [30], Sandhoff disease in Toy Poodles (0.00101) [29], and NCL in Border Collies (0.0405) [31]. Compared with the mutant allele frequencies in these lethal diseases with juvenile, late juvenile, or early adult onset [32], DM had particularly high mutant allele frequencies in PWCs (0.697) and Collies (0.138) [10,21] as well as GSDs (0.220) in this study, although there was a notably large difference in frequency among these three breeds (Table 2).…”