Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Institute of Genetics, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
J Vet Intern Med. 2024 Nov-Dec;38(6):3346-3357. doi: 10.1111/jvim.17221. Epub 2024 Oct 26.
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.
Two affected calves, their parents and 332 Chianina bulls.
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.
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%.
Genetic findings identified 2 potentially pathogenic alleles in TGDS and LAMA4, but no clear mode of inheritance could be determined.
骨骼发育不良包括一组具有遗传异质性的疾病，其特征是骨骼、关节和软骨的发育异常。我们发现了两只来自近亲交配的 Chianina 半同胞小牛，它们具有先天性骨骼畸形和心脏异常。
假说/目的：对疾病表型进行特征描述，评估其遗传原因，并确定 Chianina 群体中有害等位基因的流行率。
两只受影响的小牛、它们的父母和 332 头 Chianina 公牛。
对受影响的动物进行临床病理调查。采用全基因组测序三方法和基于 PCR 的 TDP-葡萄糖 4,6-脱水酶 (TGDS) 和层粘连蛋白亚单位 alpha 4 (LAMA4) 等位基因频率评估。
这些病例表现为生长迟缓、营养不良，伴有肌肉萎缩和后肢的角度畸形。放射学检查发现全身性骨质疏松症和肢体长骨缩短。尸检显示出骨软骨发育不良的肢体和右心室扩张。组织学检查发现，骺软骨具有软骨细胞正常柱状排列的多灶性轻度至中度丧失。还观察到骨质疏松症。遗传分析确定了 TGDS 中的错义变体和 LAMA4 中的剪接位点变体，这两个变体在 2 个病例中均为纯合子。父母为杂合子，在 Chianina 群体中，TGDS 变体的等位基因频率为 5%，LAMA4 变体的等位基因频率为 2%。
遗传发现确定了 TGDS 和 LAMA4 中的 2 个潜在致病等位基因，但无法确定明确的遗传模式。
