SGCD Missense Variant in a Lagotto Romagnolo Dog with Autosomal Recessively Inherited Limb-Girdle Muscular Dystrophy.

Brunetti, Barbara; Bacci, Barbara; Abbate, Jessica Maria; Tura, Giorgia; Paciello, Orlando; Vaccaro, Emanuela; Prisco, Francesco; Gandini, Gualtiero; Okonji, Samuel; Paola, Andrea di; Letko, Anna; Drögemüller, Cord; Jagannathan, Vidhya; Turba, Maria Elena; Ogundipe, Tolulope Grace; Lorenzini, Luca; Rosati, Marco; Psalla, Dimitra; Leeb, Tosso and Drögemüller, Michaela (2023). SGCD Missense Variant in a Lagotto Romagnolo Dog with Autosomal Recessively Inherited Limb-Girdle Muscular Dystrophy. Genes, 14(8) MDPI 10.3390/genes14081641

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An 8-month-old female Lagotto Romagnolo dog was presented for a 1-month history of an initial severe reluctance to move, rapidly progressing to a marked stiff gait and progressive muscular weakness and evolving to tetraparesis, which persuaded the owner to request euthanasia. A primary muscle pathology was supported by necropsy and histopathological findings. Macroscopically, the muscles were moderately atrophic, except for the diaphragm and the neck muscles, which were markedly thickened. Histologically, all the skeletal muscles examined showed atrophy, hypertrophy, necrosis with calcification of the fibers, and mild fibrosis and inflammation. On immunohistochemistry, all three dystrophin domains and sarcoglycan proteins were absent. On Western blot analysis, no band was present for delta sarcoglycan. We sequenced the genome of the affected dog and compared the data to more than 900 control genomes of different dog breeds. Genetic analysis revealed a homozygous private protein-changing variant in the SGCD gene encoding delta- sarcoglycan in the affected dog. The variant was predicted to induce a SGCD:p.(Leu242Pro) change in the protein. In silico tools predicted the change to be deleterious. Other 770 Lagotto Romagnolo dogs were genotyped for the variant and all found to be homozygous wild type. Based on current knowledge of gene function in other mammalian species, including humans, hamsters, and dogs, we propose the SGCD missense variant as the causative variant of the observed form of muscular dystrophy in the index case. The absence of the variant allele in the Lagotto Romagnolo breeding population indicates a rare allele that has appeared recently.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Next Generation Sequencing (NGS) Platform
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Letko, Anna, Drögemüller, Cord, Jagannathan, Vidya, Leeb, Tosso, Drögemüller, Michaela

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health

ISSN:

2073-4425

Publisher:

MDPI

Language:

English

Submitter:

Pubmed Import

Date Deposited:

30 Aug 2023 11:00

Last Modified:

07 Aug 2024 15:44

Publisher DOI:

10.3390/genes14081641

PubMed ID:

37628692

Uncontrolled Keywords:

Canis lupus familiaris Mendelian inheritance development immunohistochemistry precision medicine sarcoglycan skeletal muscle

BORIS DOI:

10.48350/185770

URI:

https://boris.unibe.ch/id/eprint/185770

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