POSTER ABSTRACTS
and a hereditary cause was suspected. Whole genome sequencing on both affected kittens was performed and the data compared to 65 genetically diverse feline genomes. By filtering for variants that were present in both kittens but absent from the control genomes, a particularly interesting candidate variant was identified. It was a homozygous missense variant in SOAT1, encoding sterol O-acyltransferase 1. The protein is localized in the endoplasmic reticulum and catalyzes the formation of cholesterol esters, an essential component of sebum. The SOAT1: c.1531G>A variant is predicted to change a highly conserved glycine residue within the last trans- membrane domain of SOAT1, p.Gly511Arg. In mice, variants in SOAT1 or complete knockout of the gene lead to the “hair interior defect” (hid) or abnormal Meibomian glands, respectively. Additional feline cases are currently being identified and samples collected to genotype the candidate variant in a larger cohort of affected and healthy cats. Further experiments are planned to evaluate the functional impact of the identified variant. #54 SH3TC2, MTMR2, and MPZ variants in Golden Retrievers with congenital hypomyelinating polyneuropathy Shawna Cook1 , Blair N Hooser1, G. Diane Shelton2, Katie Minor3, Jennifer Koziol4, Jonah N. Cullen3, Steven G. Friedenberg3, and Kari J Ekenstedt1 cook311@purdue.edu 1Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA, 2Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA, 3Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA, 4School of Veterinary Medicine, Texas Tech University, Amarillo, TX, USA Congenital hypomyelinating polyneuropathy (HPN) restricted to the peripheral nervous system was reported in 1989 in two Golden Retriever (GR) littermates. Recently, four additional cases of congenital HPN in young, minimally-related GRs were diagnosed via neurological examination, electrodiagnostic evaluation, and peripheral nerve biopsies. Whole-genome sequencing was performed on the four GRs, and variants from each dog were compared to variants found across >1,000 other dogs, representing 158 breeds, all presumably unaffected with HPN. Presumptive causative variants were identified for each HPN-affected GR. One case had a homozygous SH3TC2 nonsense variant predicted to truncate approximately one-half of the protein. Two cases shared a homozygous splice donor site variant in MTMR2, with a stop codon introduced within six codons following the inclusion of the intron. The last dog had a heterozygous MPZ missense mutation leading to an isoleucine to threonine substitution. Haplotype analysis using 524 GR established the novelty of the identified variants, with all three appearing to have emerged recently. Each variant occurs within genes that are associated with human Charcot-Marie Tooth (CMT) group of hetero- geneous diseases, affecting the peripheral nervous system. Specifically, variants within SH3TC2, MTMR2, and MPZ are associated with CMT type 4C, CMT type 4B1, and CMT type 1B, respectively. Testing a large GR population (n = >200) did not identify any dogs with these variants, confirming their nascent emergence. Although these variants are rare within the general GR population, breeders should be cautious to avoid propagating these alleles.
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