A novel ITGA2B double cytosine frameshift variant (c.1986_1987insCC) leads to Glanzmann's thrombasthenia in a cat.

Autor: Rivas VN; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA., Tan AWK; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA., Shaverdian M; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA., Nguyen NP; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA., Wouters JR; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, California, USA., Stern JA; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA., Li RHL; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Jazyk: angličtina
Zdroj: Journal of veterinary internal medicine [J Vet Intern Med] 2024 May-Jun; Vol. 38 (3), pp. 1408-1417. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1111/jvim.17030
Abstrakt: Background: Glanzmann's thrombasthenia (GT) is a congenital platelet disorder affecting approximately 1:1 000 000 people globally and characterized by impaired platelet aggregation and clot retraction. Autosomal recessive, loss-of-function, variants in ITGA2B or ITGB3 of the αIIbβ3 receptor cause the disease in humans. A cat affected by Glanzmann's and macrothrombocytopenia was presented to the UC Davis VMTH.
Hypothesis/objectives: Severe thrombopathia in this cat has an underlying genetic etiology.
Animals: A single affected patient, 2 age-matched clinically healthy controls, and a geriatric population (n = 20) of normal cats.
Methods: Physical examination and clinical pathology tests were performed on the patient. Flow cytometry and platelet aggregometry analyses for patient phenotyping were performed. Patient and validation cohort gDNA samples were extracted for Sanger sequencing of a previously identified ITGA2B (c.1986delC) variant. Reverse transcriptase PCR was performed on patient and healthy control PRP samples to verify ITGA2B variant consequence.
Results: A novel c.1986_1987insCC autosomal recessive variant in ITGA2B was identified. This variant was absent in a population of 194 unrelated cats spanning 44 different breeds. Complete loss of ITGA2B transcript and protein expression was verified by RT-PCR and flow cytometry, explaining the underlying etiology of GT, and likely macrothrombocytopenia, in this cat.
Conclusions and Clinical Importance: This study emphasizes the role of precision medicine in cardiovascular disease of cats and identified yet another variant that may be of utility for screening in the feline population. This study provides a small-volume, standardized, successful protocol for adequate platelet RNA isolation and subsequent molecular assessment of gene expression in cats.
(© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)
Databáze: MEDLINE
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