Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X-linked muscular dystrophy in a cat.
J Vet Intern Med
; 38(1): 135-144, 2024.
Article
em En
| MEDLINE
| ID: mdl-38180235
ABSTRACT
BACKGROUND:
Muscular dystrophies (MDs) are a large, heterogeneous group of degenerative muscle diseases. X-linked dystrophin-deficient MD in cats is the first genetically characterized cat model for a human disease and a few novel forms have been identified. HYPOTHESIS/OBJECTIVES:
Muscular dystrophy was suspected in a young male domestic shorthair cat. Clinical, molecular, and genetic techniques could provide a definitive diagnosis. ANIMALS A 1-year-old male domestic shorthair cat presented for progressive difficulty walking, macroglossia and dysphagia beginning at 6 months of age. The tongue was thickened, protruded with constant ptyalism, and thickening and rigidity of the neck and shoulders were observed.METHODS:
A complete neurological examination, baseline laboratory evaluation and biopsies of the trapezius muscle were performed with owner consent. Indirect immunofluorescence staining of muscle cryosections was performed using several monoclonal and polyclonal antibodies against dystrophy-associated proteins. DNA was isolated for genomic analyses by whole genome sequencing and comparison to DNA variants in the 99 Lives Cat Genome Sequencing dataset. RESULTS AND CLINICAL IMPORTANCE Aspartate aminotransferase (687 IU/L) and creatine kinase (24 830 IU/L) activities were increased and mild hypokalemia (3.7 mmol/L) was present. Biopsy samples from the trapezius muscle confirmed a degenerative and regenerative myopathy and protein alterations identified by immunohistochemistry resulted in a diagnosis of a in dystrophin-deficient form of X-linked MD. A stop gain variant (c.4849C>T; p.Gln1617Ter) dystrophin was identified by genome sequencing. Precision/genomic medicine efforts for the domestic cat and in veterinary medicine support disease variant and animal model discovery and provide opportunities for targeted treatments for companion animals.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças do Gato
/
Distrofia Muscular de Duchenne
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Vet Intern Med
Assunto da revista:
MEDICINA INTERNA
/
MEDICINA VETERINARIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos