A homozygous PIGN missense mutation in Soft-Coated Wheaten Terriers with a canine paroxysmal dyskinesia.

Autor: Kolicheski AL; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., Johnson GS; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., Mhlanga-Mutangadura T; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA., Taylor JF; Division of Animal Sciences, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, MO, USA., Schnabel RD; Division of Animal Sciences, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, MO, USA.; Informatics Institute, University of Missouri, Columbia, MO, USA., Kinoshita T; Department of Immunoregulation, Research Institute for Microbial Diseases, and Laboratory of Immunoglycobiology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan., Murakami Y; Department of Immunoregulation, Research Institute for Microbial Diseases, and Laboratory of Immunoglycobiology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan., O'Brien DP; Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA. obriend@missouri.edu.
Jazyk: angličtina
Zdroj: Neurogenetics [Neurogenetics] 2017 Jan; Vol. 18 (1), pp. 39-47. Date of Electronic Publication: 2016 Nov 28.
DOI: 10.1007/s10048-016-0502-4
Abstrakt: Hereditary paroxysmal dyskinesias (PxD) are a heterogeneous group of movement disorders classified by frequency, duration, and triggers of the episodes. A young-adult onset canine PxD has segregated as an autosomal recessive trait in Soft-Coated Wheaten Terriers. The medical records and videos of episodes from 25 affected dogs were reviewed. The episodes of hyperkinesia and dystonia lasted from several minutes to several hours and could occur as often as >10/day. They were not associated with strenuous exercise or fasting but were sometimes triggered by excitement. The canine PxD phenotype most closely resembled paroxysmal non-kinesigenic dyskinesia (PNKD) of humans. Whole genome sequences were generated with DNA from 2 affected dogs and analyzed in comparison to 100 control canid whole genome sequences. The two whole genome sequences from dogs with PxD had a rare homozygous PIGN:c.398C > T transition, which predicted the substitution of an isoleucine for a highly conserved threonine in the encoded enzyme. All 25 PxD-affected dogs were PIGN:c.398T allele homozygotes, whereas there were no c.398T homozygotes among 1185 genotyped dogs without known histories of PxD. PIGN encodes an enzyme involved in the biosynthesis of glycosylphosphatidylinositol (GPI), which anchors a variety of proteins including CD59 to the cell surface. Flow cytometry of PIGN-knockout HEK239 cells expressing recombinant human PIGN with the c.398T variant showed reduced CD59 expression. Mutations in human PIGN have been associated with multiple congenital anomalies-hypotonia-seizures syndrome-1 (MCAHS1). Movement disorders can be a part of MCAHS1, but this is the first PxD associated with altered GPI anchor function.
Competing Interests: The authors declare that they have no conflict of interest. Ethical approval All studies were approved by the University of Missouri Animal Care and Use Committee, and informed consent was obtained from the dogs’ owners.
Databáze: MEDLINE
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