Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat
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 dy...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
|
| Series: | Journal of Veterinary Internal Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jvim.16971 |
| _version_ | 1797349551795863552 |
|---|---|
| author | G. Diane Shelton Fabrizio Tucciarone Ling T. Guo Lyndon M. Coghill Leslie A. Lyons |
| author_facet | G. Diane Shelton Fabrizio Tucciarone Ling T. Guo Lyndon M. Coghill Leslie A. Lyons |
| author_sort | G. Diane Shelton |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T12:31:57Z |
| format | Article |
| id | doaj.art-09b39a86188e450caec7328ebde389b7 |
| institution | Directory Open Access Journal |
| issn | 0891-6640 1939-1676 |
| language | English |
| last_indexed | 2024-03-08T12:31:57Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Veterinary Internal Medicine |
| spelling | doaj.art-09b39a86188e450caec7328ebde389b72024-01-22T02:05:50ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762024-01-0138113514410.1111/jvim.16971Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a catG. Diane Shelton0Fabrizio Tucciarone1Ling T. Guo2Lyndon M. Coghill3Leslie A. Lyons4Department of Pathology, School of Medicine University of California San Diego La Jolla California USAAbington Park Vets Referrals Northampton United KingdomDepartment of Pathology, School of Medicine University of California San Diego La Jolla California USADepartment of Veterinary Pathobiology, College of Veterinary Medicine University of Missouri Columbia Missouri USADepartment of Veterinary Pathobiology, College of Veterinary Medicine University of Missouri Columbia Missouri USAAbstract 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.https://doi.org/10.1111/jvim.16971animal modelsFelis catusprecision medicinewhole genome sequencing |
| spellingShingle | G. Diane Shelton Fabrizio Tucciarone Ling T. Guo Lyndon M. Coghill Leslie A. Lyons Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat Journal of Veterinary Internal Medicine animal models Felis catus precision medicine whole genome sequencing |
| title | Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat |
| title_full | Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat |
| title_fullStr | Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat |
| title_full_unstemmed | Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat |
| title_short | Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat |
| title_sort | precision medicine using whole genome sequencing identifies a novel dystrophin dmd variant for x linked muscular dystrophy in a cat |
| topic | animal models Felis catus precision medicine whole genome sequencing |
| url | https://doi.org/10.1111/jvim.16971 |
| work_keys_str_mv | AT gdianeshelton precisionmedicineusingwholegenomesequencingidentifiesanoveldystrophindmdvariantforxlinkedmusculardystrophyinacat AT fabriziotucciarone precisionmedicineusingwholegenomesequencingidentifiesanoveldystrophindmdvariantforxlinkedmusculardystrophyinacat AT lingtguo precisionmedicineusingwholegenomesequencingidentifiesanoveldystrophindmdvariantforxlinkedmusculardystrophyinacat AT lyndonmcoghill precisionmedicineusingwholegenomesequencingidentifiesanoveldystrophindmdvariantforxlinkedmusculardystrophyinacat AT lesliealyons precisionmedicineusingwholegenomesequencingidentifiesanoveldystrophindmdvariantforxlinkedmusculardystrophyinacat |