Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle

Abstract Background Skeletal dysplasia encompasses a heterogeneous group of genetic disorders characterized by an abnormal development of bones, joints, and cartilage. Two Chianina half‐sibling calves from consanguineous mating with congenital skeletal malformations and cardiac abnormalities were id...

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Main Authors: Joana G. P. Jacinto, Tolulope G. Ogundipe, Cinzia Benazzi, Irene M. Häfliger, Luisa V. Muscatello, Marilena Bolcato, Riccardo Rinnovati, Arcangelo Gentile, Cord Drögemüller
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Journal of Veterinary Internal Medicine
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Online Access:https://doi.org/10.1111/jvim.17221
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author Joana G. P. Jacinto
Tolulope G. Ogundipe
Cinzia Benazzi
Irene M. Häfliger
Luisa V. Muscatello
Marilena Bolcato
Riccardo Rinnovati
Arcangelo Gentile
Cord Drögemüller
author_facet Joana G. P. Jacinto
Tolulope G. Ogundipe
Cinzia Benazzi
Irene M. Häfliger
Luisa V. Muscatello
Marilena Bolcato
Riccardo Rinnovati
Arcangelo Gentile
Cord Drögemüller
author_sort Joana G. P. Jacinto
collection DOAJ
description Abstract Background Skeletal dysplasia encompasses a heterogeneous group of genetic disorders characterized by an abnormal development of bones, joints, and cartilage. Two Chianina half‐sibling calves from consanguineous mating with congenital skeletal malformations and cardiac abnormalities were identified. Hypothesis/Objectives To characterize the disease phenotype, to evaluate its genetic cause, and to determine the prevalence of the deleterious alleles in the Chianina population. Animals Two affected calves, their parents and 332 Chianina bulls. Methods The affected animals underwent clinicopathological investigation. Whole‐genome sequencing trio‐approach and PCR‐based assessment of the frequency of TDP‐glucose 4,6‐dehydratase (TGDS) and laminin subunit alpha 4 (LAMA4) alleles were performed. Results The cases presented with retarded growth, poor nutritional status associated with muscular atrophy and angular deformities of the hindlimbs. Radiologic examination identified generalized osteopenia and shortening of the limb long bones. Necropsy showed osteochondrodysplastic limbs and dilatation of the heart right ventricle. On histological examination, the physeal cartilages were characterized by multifocal mild to moderate loss of the normal columnar arrangement of chondrocytes. Osteopenia also was observed. Genetic analysis identified a missense variant in TGDS and a splice‐site variant in LAMA4, both of which were homozygous in the 2 cases. Parents were heterozygous and allele frequency in the Chianina population for the TGDS variant was 5% and for the LAMA4 variant was 2%. Conclusions and Clinical Importance Genetic findings identified 2 potentially pathogenic alleles in TGDS and LAMA4, but no clear mode of inheritance could be determined.
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spelling doaj-art-e710b8bb9ef54556b793bd3e00d4fdb02025-08-20T01:53:30ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762024-11-013863346335710.1111/jvim.17221Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattleJoana G. P. Jacinto0Tolulope G. Ogundipe1Cinzia Benazzi2Irene M. Häfliger3Luisa V. Muscatello4Marilena Bolcato5Riccardo Rinnovati6Arcangelo Gentile7Cord Drögemüller8Department of Veterinary Medical Sciences University of Bologna Bologna ItalyDepartment of Veterinary Medical Sciences University of Bologna Bologna ItalyDepartment of Veterinary Medical Sciences University of Bologna Bologna ItalyInstitute of Genetics, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty University of Bern Bern SwitzerlandDepartment of Veterinary Medical Sciences University of Bologna Bologna ItalyDepartment of Veterinary Medical Sciences University of Bologna Bologna ItalyDepartment of Veterinary Medical Sciences University of Bologna Bologna ItalyDepartment of Veterinary Medical Sciences University of Bologna Bologna ItalyInstitute of Genetics, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty University of Bern Bern SwitzerlandAbstract Background Skeletal dysplasia encompasses a heterogeneous group of genetic disorders characterized by an abnormal development of bones, joints, and cartilage. Two Chianina half‐sibling calves from consanguineous mating with congenital skeletal malformations and cardiac abnormalities were identified. Hypothesis/Objectives To characterize the disease phenotype, to evaluate its genetic cause, and to determine the prevalence of the deleterious alleles in the Chianina population. Animals Two affected calves, their parents and 332 Chianina bulls. Methods The affected animals underwent clinicopathological investigation. Whole‐genome sequencing trio‐approach and PCR‐based assessment of the frequency of TDP‐glucose 4,6‐dehydratase (TGDS) and laminin subunit alpha 4 (LAMA4) alleles were performed. Results The cases presented with retarded growth, poor nutritional status associated with muscular atrophy and angular deformities of the hindlimbs. Radiologic examination identified generalized osteopenia and shortening of the limb long bones. Necropsy showed osteochondrodysplastic limbs and dilatation of the heart right ventricle. On histological examination, the physeal cartilages were characterized by multifocal mild to moderate loss of the normal columnar arrangement of chondrocytes. Osteopenia also was observed. Genetic analysis identified a missense variant in TGDS and a splice‐site variant in LAMA4, both of which were homozygous in the 2 cases. Parents were heterozygous and allele frequency in the Chianina population for the TGDS variant was 5% and for the LAMA4 variant was 2%. Conclusions and Clinical Importance Genetic findings identified 2 potentially pathogenic alleles in TGDS and LAMA4, but no clear mode of inheritance could be determined.https://doi.org/10.1111/jvim.17221bovineinbreedinglethal allele frequencyprecision medicinerecessive disorders
spellingShingle Joana G. P. Jacinto
Tolulope G. Ogundipe
Cinzia Benazzi
Irene M. Häfliger
Luisa V. Muscatello
Marilena Bolcato
Riccardo Rinnovati
Arcangelo Gentile
Cord Drögemüller
Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle
Journal of Veterinary Internal Medicine
bovine
inbreeding
lethal allele frequency
precision medicine
recessive disorders
title Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle
title_full Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle
title_fullStr Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle
title_full_unstemmed Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle
title_short Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle
title_sort familial osteochondrodysplastic and cardiomyopathic syndrome in chianina cattle
topic bovine
inbreeding
lethal allele frequency
precision medicine
recessive disorders
url https://doi.org/10.1111/jvim.17221
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