A de novo nonsense variant in the DMD gene associated with X-linked dystrophin-deficient muscular dystrophy in a cat.

Autor: Yokoyama N; Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan., Matsumoto Y; Anicom Insurance, Inc., Tokyo, Japan., Yamaguchi T; Veterinary Teaching Hospital, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan., Okada K; North Lab, Sapporo, Japan., Kinoshita R; Veterinary Teaching Hospital, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan., Shimbo G; Veterinary Teaching Hospital, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan., Ukawa H; Anicom Insurance, Inc., Tokyo, Japan., Ishii R; Anicom Insurance, Inc., Tokyo, Japan., Nakamura K; Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan., Yamazaki J; Translational Research Unit, Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.; One Health Research Center, Hokkaido University, Sapporo, Hokkaido, Japan., Takiguchi M; Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.; One Health Research Center, Hokkaido University, Sapporo, Hokkaido, Japan.
Jazyk: angličtina
Zdroj: Journal of veterinary internal medicine [J Vet Intern Med] 2024 May-Jun; Vol. 38 (3), pp. 1418-1424. Date of Electronic Publication: 2024 Apr 13.
DOI: 10.1111/jvim.17078
Abstrakt: Background: X-linked dystrophin-deficient muscular dystrophy (MD) is a form of MD caused by variants in the DMD gene. It is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles.
Hypothesis/objectives: Identify deleterious genetic variants in DMD by whole-genome sequencing (WGS) using a next-generation sequencer.
Animals: One MD-affected cat, its parents, and 354 cats from a breeding colony.
Methods: We compared the WGS data of the affected cat with data available in the National Center for Biotechnology Information database and searched for candidate high-impact variants by in silico analyses. Next, we confirmed the candidate variants by Sanger sequencing using samples from the parents and cats from the breeding colony. We used 2 genome assemblies, the standard felCat9 (from an Abyssinian cat) and the novel AnAms1.0 (from an American Shorthair cat), to evaluate genome assembly differences.
Results: We found 2 novel high-impact variants: a 1-bp deletion in felCat9 and an identical nonsense variant in felCat9 and AnAms1.0. Whole genome and Sanger sequencing validation showed that the deletion in felCat9 was a false positive because of misassembly. Among the 357 cats, the nonsense variant was only found in the affected cat, which indicated it was a de novo variant.
Conclusion and Clinical Importance: We identified a de novo variant in the affected cat and next-generation sequencing-based genotyping of the whole DMD gene was determined to be necessary for affected cats because the parents of the affected cat did not have the risk variant.
(© 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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