MFSD8 single base pair deletion in a Chihuahua with neuronal ceroid lipofuscinosis. CH019

Background: Variants in MFSD8 encoding “major facilitator superfamily domain containing 8” are responsible for neuronal ceroid lipofuscinosis 7 (NCL7) in humans (OMIM #610951)1. Two recent reports identified a single base deletion in MFSD8, c.843delT, in Chinese Crested dogs2 and Chihuahuas3 with NCL7. Own analysis: Independently from the two previously published canine studies2,3, we investigated a litter of Chihuahuas, in which one puppy had clear signs of NCL (File S1) and was euthanized due to the poor prognosis of this neurodegenerative disease. The dogs did not have official registration papers from the Swiss Kennel Club (SKG). We sequenced the genome of the affected puppy with 2x150 bp paired-end reads on an illumina Hiseq 3000 instrument. We mapped the reads to the CanFam 3.1 reference genome yielding 31.5x average genome coverage. We called variants as described4 and compared them to variants from 274 control dog genomes. The affected Chihuahua had 17 private non-synonymous homozygous variants in the genome including the earlier reported MFSD8:c.843delT variant. We confirmed the presence of the variant by Sanger sequencing. The affected Chihuahua was homozygous mutant. Its mother was heterozygous as expected for an obligate carrier of a monogenic autosomal recessive trait. Comments: Using WGS data we identified an MFSD8 frame-shift variant in a Chihuahua with a neuronal ceroid lipofuscinosis. Our findings confirm two recently published reports identifying the same variant in Chinese Crested dogs and Chihuahuas with NCL7