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Hum Genet. 2019 Mar 7. doi: 10.1007/s00439-019-01986-x. [Epub ahead of print]

A glycine transporter SLC6A5 frameshift mutation causes startle disease in Spanish greyhounds.

Author information

1
Department of Genetics and Biochemistry, Clemson University, Clemson, SC, 29634, USA.
2
Fundació Hospital Clínic Veterinari, Universitat Autònoma de Barcelona, Bellaterra, Spain.
3
Clinica Veterinaria Levante, San Javier, Murcia, Spain.
4
Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
5
Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. gshelton@ucsd.edu.
6
Department of Genetics and Biochemistry, Clemson University, Clemson, SC, 29634, USA. lclark4@clemson.edu.

Abstract

Startle disease, or hyperekplexia, is a glycinergic disorder characterized by hypertonia and apnea that is triggered by noise and/or touch. Mutations in five genes have been associated with startle disease in humans, dogs, cattle, and mice. We identified a novel recessive startle disease in a family of Spanish greyhounds. Whole genome resequencing of an affected dog revealed a homozygous two base pair deletion in the ninth exon of SLC6A5, encoding the presynaptic glycine transporter. The deletion is predicted to cause a frameshift, p.S460FfsX47, leading to a premature stop codon that truncates over a third of the protein. Family members were genotyped for the deletion, and findings were consistent with an autosomal recessive inheritance pattern. The pathogenic variant was absent from 34 unrelated greyhounds, 659 domestic dogs of pure and mixed breeds, and 54 wild canids, suggesting it occurred recently and may be private to the family. The findings of this study can be used to inform future breeding decisions and prevent dissemination of the deleterious allele in greyhounds.

PMID:
30847549
DOI:
10.1007/s00439-019-01986-x

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