{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T19:55:51Z","timestamp":1785009351142,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Two Shiba Inu littermates presented for investigation of marked and persistent elevation of creatine kinase activities. Method and Results: Histopathology of muscle biopsy samples revealed a dystrophic phenotype and immunostaining confirmed an absence of dystrophin protein in both cases. Whole genome sequencing of one affected dog revealed a complex deletion in the DMD gene encompassing exon 5. Screening of 27 related dogs confirmed an X-linked inheritance. The variant was identified in three related male dogs. One littermate died from cardiac arrest and the other littermate had no clinical myopathic signs at the time of the manuscript\u2019s preparation. An additional related male dog reportedly died suddenly during grooming. Conclusion: This study adds a new breed to the canine dystrophinopathy spectrum having a ~17 kb deletion that encompasses exon 5 of DMD. This same exon 5 deletion has been identified in human dystrophin-deficient muscular dystrophy patients.<\/jats:p>","DOI":"10.3390\/genes16111369","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:56:27Z","timestamp":1762858587000},"page":"1369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dystrophin-Deficient Muscular Dystrophy in a Family of Shiba Inu Dogs with a Complex Deletion Encompassing DMD Exon 5"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6992-6634","authenticated-orcid":false,"given":"Laura","family":"Mcleay","sequence":"first","affiliation":[{"name":"Small Animal Specialist Hospital, North Ryde 2113, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Hardinge","sequence":"additional","affiliation":[{"name":"Melbourne Veterinary Specialist Centre, Glen Waverley, Victoria 3250, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5472-5088","authenticated-orcid":false,"given":"Katie M.","family":"Minor","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7510-2322","authenticated-orcid":false,"given":"Steven G.","family":"Friedenberg","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonah N.","family":"Cullen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling T.","family":"Guo","sequence":"additional","affiliation":[{"name":"Comparative Neuromuscular Laboratory, Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3332-1359","authenticated-orcid":false,"given":"G. Diane","family":"Shelton","sequence":"additional","affiliation":[{"name":"Comparative Neuromuscular Laboratory, Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2344\/673191","article-title":"A Review of Muscular Dystrophies","volume":"71","author":"Hoang","year":"2024","journal-title":"Anesth. Prog."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S1474-4422(03)00585-4","article-title":"Dystrophin and mutations: One gene, several proteins, multiple phenotypes","volume":"2","author":"Muntoni","year":"2003","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/jsap.12292","article-title":"Dystrophin-deficient muscular dystrophy in a Norfolk terrier","volume":"56","author":"Beltran","year":"2015","journal-title":"J. Small Anim. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1292\/jvms.21-0504","article-title":"Dystrophin-deficient muscular dystrophy in a Toy Poodle with a single base pair insertion in exon 45 of the Duchenne muscular dystrophy gene","volume":"84","author":"Sakai","year":"2022","journal-title":"J. Vet. Med. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"292","DOI":"10.5326\/JAAHA-MS-7255","article-title":"Dystrophin-Deficient Muscular Dystrophy in Two Male Juvenile Brittanys","volume":"58","author":"Stevens","year":"2022","journal-title":"J. Am. Anim. Hosp. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13395-017-0124-z","article-title":"The golden retriever model of Duchenne muscular dystrophy","volume":"7","author":"Kornegay","year":"2017","journal-title":"Skelet. Muscle"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13395-020-00239-0","article-title":"X-linked muscular dystrophy in a Labrador Retriever strain: Phenotypic and molecular characterisation","volume":"10","author":"Calmels","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13023-020-01430-8","article-title":"Global epidemiology of Duchenne muscular dystrophy: An updated systematic review and meta-analysis","volume":"15","author":"Crisafulli","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shelton, G.D., Minor, K.M., Friedenberg, S.G., Cullen, J.N., Guo, L.T., and Mickelson, J.R. (2023). Current Classification of Canine Muscular Dystrophies and Identification of New Variants. Genes, 14.","DOI":"10.3390\/genes14081557"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1292\/jvms.17-0459","article-title":"Electrophysiological and histopathological findings of muscular disease suspected as myotonic dystrophy in a Shiba dog","volume":"80","author":"Shiga","year":"2018","journal-title":"J. Vet. Med. Sci."},{"key":"ref_11","unstructured":"Dubowitz, V., Sewry, C.A., and Oldfors, A. (2021). Histological and histochemical stains and reactions. Muscle Biopsy: A Practical Approach, Elsevier. [5th ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.nmd.2010.07.278","article-title":"Evaluation of commercial dysferlin antibodies on canine, mouse and human skeletal muscle","volume":"20","author":"Guo","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38171","DOI":"10.1074\/jbc.274.53.38171","article-title":"Sarcoglycan isoforms in skeletal muscle","volume":"274","author":"Liu","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1073\/pnas.85.5.1544","article-title":"Merosin, a protein specific for basement membranes of Schwann cells, striated muscle, and trophoblast, is expressed late in nerve and muscle development","volume":"85","author":"Leivo","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1016\/S0021-9258(17)43189-9","article-title":"Type VI collagen. Studies on its localization, structure and biosynthetic form with monoclonal antibodies","volume":"259","author":"Hessle","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, C., Wallerman, O., Arendt, M.-L., Sundstr\u00f6m, E., Karlsson, \u00c5., Nordin, J., M\u00e4kel\u00e4inen, S., Pielberg, G.R., Hanson, J., and Ohlsson, \u00c5. (2021). A novel canine reference genome resolves genomic architecture and uncovers transcript complexity. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-01698-x"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Meadows, J.R., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., and Hitte, C. (2023). Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol., 24.","DOI":"10.1186\/s13059-023-03023-7"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"jkad117","DOI":"10.1093\/g3journal\/jkad117","article-title":"Whole animal genome sequencing: User-friendly, rapid, containerized pipelines for processing, variant discovery, and annotation of short-read whole genome sequencing data","volume":"13","author":"Cullen","year":"2023","journal-title":"G3"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"McLaren, W., Gil, L., Hunt, S.E., Riat, H.S., Ritchie, G.R.S., Thormann, A., Flicek, P., and Cunningham, F. (2016). The Ensembl Variant Effect Predictor. Genome Biol., 17.","DOI":"10.1186\/s13059-016-0974-4"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Toh, Z.Y., Thandar Aung-Htut, M., Pinniger, G., Adams, A.M., Krishnaswarmy, S., Wong, B.L., Fletcher, S., and Wilton, S.D. (2016). Deletion of Dystrophin In-Frame Exon 5 Leads to a Severe Phenotype: Guidance for Exon Skipping Strategies. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0145620"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1111\/jvim.15073","article-title":"A de novo mutation in the EXT2 gene associated with osteochondromatosis in a litter of American Staffordshire Terriers","volume":"32","author":"Friedenberg","year":"2018","journal-title":"J. Vet. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.nmd.2022.08.001","article-title":"Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype","volume":"32","author":"Shelton","year":"2022","journal-title":"Neuromuscul. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/ilar\/ilu011","article-title":"Pharmacologic management of Duchenne muscular dystrophy: Target identification and preclinical trials","volume":"55","author":"Kornegay","year":"2014","journal-title":"ILAR J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jns.2013.09.036","article-title":"Symptomatic female carriers of Duchenne muscular dystrophy (DMD): Genetic and clinical characterization","volume":"336","author":"Giliberto","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"00176","DOI":"10.1183\/23120541.00176-2023","article-title":"Cardiomyopathy as cause of death in Duchenne muscular dystrophy: A longitudinal observational study","volume":"9","author":"Lechner","year":"2023","journal-title":"ERJ Open Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27089","DOI":"10.31083\/RCM27089","article-title":"Arrhythmic Risk Stratification and Sudden Cardiac Death Prevention in Duchenne Muscular Dystrophy: A Critical Appraisal","volume":"26","author":"Arcudi","year":"2025","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e012443","DOI":"10.1161\/JAHA.119.012443","article-title":"Natural History of Cardiomyopathy in Adult Dogs with Golden Retriever Muscular Dystrophy","volume":"8","author":"Guo","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/mus.27522","article-title":"Serum cardiac troponin I is a candidate biomarker for cardiomyopathy in Duchenne and Becker muscular dystrophies","volume":"65","author":"Yamaguchi","year":"2022","journal-title":"Muscle Nerve"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0034-5288(91)90067-X","article-title":"Hereditary high-potassium erythrocytes with high Na, K-ATPase activity in Japanese shiba dogs","volume":"50","author":"Maede","year":"1991","journal-title":"Res. Vet. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/pan.12248","article-title":"Anesthesia and Duchenne or Becker muscular dystrophy: Review of 117 anesthetic exposures","volume":"23","author":"Segura","year":"2013","journal-title":"Paediatr. Anesth."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/11\/1369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:09:22Z","timestamp":1762859362000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/11\/1369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["genes16111369"],"URL":"https:\/\/doi.org\/10.3390\/genes16111369","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]}}}