Startle disease in Irish wolfhounds associated with a microdeletion in the glycine transporter GlyT2 gene

J L Gill; D Capper; J F Vanbellinghen; S K Chung; R J Higgins; M I Rees; G D Shelton; Robert J Harvey

doi:10.1016/j.nbd.2011.03.010

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Startle disease in Irish wolfhounds associated with a microdeletion in the glycine transporter GlyT2 gene

Journal article

Open access

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Startle disease in Irish wolfhounds associated with a microdeletion in the glycine transporter GlyT2 gene

J L Gill, D Capper, J F Vanbellinghen, S K Chung, R J Higgins, M I Rees, G D Shelton and Robert J Harvey

Neurobiology of Disease, Vol.43(1), pp.184-189

2011

DOI: https://doi.org/10.1016/j.nbd.2011.03.010

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Abstract

glycine transporter

GlyT2

hyperekplexia

irish wolfhound

SLC6A5

startle disease

Defects in glycinergic synaptic transmission in humans, cattle, and rodents result in an exaggerated startle reflex and hypertonia in response to either acoustic or tactile stimuli. Molecular genetic studies have determined that mutations in the genes encoding the postsynaptic glycine receptor (GlyR) ?1 and ? subunits (GLRA1 and GLRB) and the presynaptic glycine transporter GlyT2 (SLC6A5) are the major cause of these disorders. Here, we report the first genetically confirmed canine cases of startle disease. A litter of seven Irish wolfhounds was identified in which two puppies developed muscle stiffness and tremor in response to handling. Although sequencing of GLRA1 and GLRB did not reveal any pathogenic mutations, analysis of SLC6A5 revealed a homozygous 4.2. kb microdeletion encompassing exons 2 and 3 in both affected animals. This results in the loss of part of the large cytoplasmic N-terminus and all subsequent transmembrane domains due to a frameshift. This genetic lesion was confirmed by defining the deletion breakpoint, Southern blotting, and multiplex ligation-dependent probe amplification (MLPA). This analysis enabled the development of a rapid genotyping test that revealed heterozygosity for the deletion in the dam and sire and three other siblings, confirming recessive inheritance. Wider testing of related animals has identified a total of 13 carriers of the SLC6A5 deletion as well as non-carrier animals. These findings will inform future breeding strategies and enable a rational pharmacotherapy of this new canine disorder. © 2011 Elsevier Inc.

Details

Title: Startle disease in Irish wolfhounds associated with a microdeletion in the glycine transporter GlyT2 gene
Authors: J L Gill (Author) - University College London, United Kingdom
D Capper (Author) - Halsey East Animal Clinic, United States
J F Vanbellinghen (Author) - Centre Hospitalier Universitaire de Liège, Belgium
S K Chung (Author) - Swansea University, United Kingdom
R J Higgins (Author) - University of California, United States
M I Rees (Author) - Swansea University, United Kingdom
G D Shelton (Author) - University of California, United States
Robert J Harvey (Author) - University College London, United Kingdom
Publication details: Neurobiology of Disease, Vol.43(1), pp.184-189
Publisher: Academic Press
Date published: 2011
DOI: 10.1016/j.nbd.2011.03.010
ISSN: 0969-9961
Copyright note: Copyright © Gill et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 License.
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99451050302621
Output Type: Journal article

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