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

• Published in: Genes
• Main Authors: Barbara Brunetti, Barbara Bacci, Jessica Maria Abbate, Giorgia Tura, Orlando Paciello, Emanuela Vaccaro, Francesco Prisco, Gualtiero Gandini, Samuel Okonji, Andrea di Paola, Anna Letko, Cord Drögemüller, Vidhya Jagannathan, Maria Elena Turba, Tolulope Grace Ogundipe, Luca Lorenzini, Marco Rosati, Dimitra Psalla, Tosso Leeb, Michaela Drögemüller
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2023
• Subjects: sarcoglycan; Canis lupus familiaris; skeletal muscle; immunohistochemistry; precision medicine; Mendelian inheritance; Genetics; QH426-470; Canis lupus
• Online Access: https://doi.org/10.3390/genes14081641; https://doaj.org/article/b537e698baac4c42812e3fc0162e3188

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.