A de novo nonsense variant in the DMD gene associated with X-linked dystrophin-deficient muscular dystrophy in a cat.
J Vet Intern Med
; 38(3): 1418-1424, 2024.
Article
em En
| MEDLINE
| ID: mdl-38613437
ABSTRACT
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças do Gato
/
Distrofina
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Distrofia Muscular Animal
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article