Jacinto Joana G P, Häfliger Irene M, McEvoy Fintan J, Drögemüller Cord, Agerholm Jørgen S
Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy.
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
Animals (Basel). 2021 Feb 20;11(2):561. doi: 10.3390/ani11020561.
Osteogenesis imperfecta (OI) type II is a genetic connective tissue disorder characterized by bone fragility, severe skeletal deformities and shortened limbs. OI usually causes perinatal death of affected individuals. OI type II diagnosis in humans is established by the identification of heterozygous mutations in genes coding for collagens. The purpose of this study was to characterize the pathological phenotype of an OI type II-affected neonatal Holstein calf and to identify the causative genetic variant by whole-genome sequencing (WGS). The calf had acute as well as intrauterine fractures, abnormally shaped long bones and localized arthrogryposis. Genetic analysis revealed a private heterozygous missense variant in (c.3917T>A) located in the fibrillar collagen NC1 domain (p.Val1306Glu) that most likely occurred de novo. This confirmed the diagnosis of OI type II and represents the first report of a pathogenic variant in the fibrillar collagen NC domain of associated to OI type II in domestic animals. Furthermore, this study highlights the utility of WGS-based precise diagnostics for understanding congenital disorders in cattle and the need for continued surveillance for rare lethal genetic disorders in cattle.
II型成骨不全症（OI）是一种遗传性结缔组织疾病，其特征为骨骼脆弱、严重骨骼畸形和肢体短小。OI通常导致受影响个体围产期死亡。人类II型OI的诊断是通过鉴定编码胶原蛋白的基因中的杂合突变来确定的。本研究的目的是表征一头受II型OI影响的新生荷斯坦犊牛的病理表型，并通过全基因组测序（WGS）鉴定致病基因变异。该犊牛有急性骨折以及子宫内骨折、长骨形状异常和局部关节挛缩。遗传分析揭示了位于纤维状胶原蛋白NC1结构域（c.3917T>A）中的一个私有的杂合错义变异（p.Val1306Glu），该变异很可能是新生突变。这证实了II型OI的诊断，并代表了家畜中与II型OI相关的纤维状胶原蛋白NC结构域中致病变异的首次报道。此外，本研究强调了基于WGS的精确诊断对于理解牛先天性疾病的实用性，以及对牛罕见致死性遗传疾病持续监测的必要性。
