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Precision medicine identifies a pathogenic variant of the ITGA2B gene responsible for Glanzmann's thrombasthenia in a cat2.04 MB
Published VersionCC BY-NC V4.0, Open Access
Journal article
Precision medicine identifies a pathogenic variant of the ITGA2B gene responsible for Glanzmann's thrombasthenia in a cat
Journal of Veterinary Internal Medicine, Vol.34(6), pp.2438-2446
2020
PMID: 32935881
Abstract
Background:
A nonpedigreed male cat presented with epistaxis, severe bladder hemorrhage, and secondary urethral obstruction after cystocentesis.
Objectives:
To characterize the phenotype of a cat with bleeding diathesis and use a precision medicine approach to identify the molecular genetic defect by whole genome sequencing.
Methods:
Adenosine diphosphate (ADP) and arachidonic acid (AA)‐induced whole blood platelet aggregometry was performed in the affected cat and a healthy cat. Platelet activation, measured by P‐selectin expression, and surface integrin subunit β3 expression were evaluated by flow cytometry in the affected cat and healthy control. Total integrin subunit αIIb expression was assessed by western blot. Whole genome sequencing at 30× coverage was used to identify genetic variants that segregated in the affected cat compared to 194 cats from the 99 Lives Sequencing Consortium.
Results:
Platelet aggregometry identified significant impairment in platelet aggregation in response to ADP and AA compared to the control cat. Targeted protein expression analyses by flow cytometry and immunoblot analysis determined that the surface expression and total expression of the integrin, αIIbβ3, was absent. Whole genome sequencing identified a homozygous c.1986delC frameshift variant in the integrin subunit αIIb (ITGA2B) gene that was not detected in the control population. The p.Pro662fs (ITGA2B P662X) variant terminates translation of the protein at the extracellular domain of the integrin prematurely, which is predicted to affect expression of the β3 unit.
Conclusions and Clinical Importance:
This novel ITGA2B variant and the associated phenotype closely resemble Glanzmann's thrombasthenia, which has never been reported in cats.
Details
- Title
- Precision medicine identifies a pathogenic variant of the ITGA2B gene responsible for Glanzmann's thrombasthenia in a cat
- Authors
- Ronald H. L Li (Corresponding Author) - University of California, DavisEric Ontiveros (Author) - University of California, DavisNghi Nguyen (Author) - University of California, DavisJoshua A Stern (Author) - University of California, DavisElizabeth Lee (Author) - University of California, DavisBrian T Hardy (Author) - University of California, Davis99 Lives Cat Genome Consortium (Research Group)Robert Harvey (Consortium Member) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
- Publication details
- Journal of Veterinary Internal Medicine, Vol.34(6), pp.2438-2446; 9
- Publisher
- John Wiley & Sons, Inc
- Date published
- 2020
- DOI
- 10.1111/jvim.15886
- ISSN
- 1939-1676; 0891-6640
- PMID
- 32935881
- Copyright note
- © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in anymedium, provided the original work is properly cited and is not used for commercial purposes.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99569408802621
- Output Type
- Journal article
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