Bolcato Marilena, Romito Giovanni, Häfliger Irene M, Gentile Arcangelo, Drögemüller Cord, Jacinto Joana G P
Department of Veterinary Medical Sciences, University of Bologna, Ozzano, Italy.
Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
J Vet Intern Med. 2025 Jul-Aug;39(4):e70144. doi: 10.1111/jvim.70144.
Cleft palate (CP) is a congenital defect characterized by an opening in the palate. Two crossbred paternal half-sibs with a complex syndrome including CP were identified.
HYPOTHESIS/OBJECTIVES: Characterize disease phenotype and evaluate the genetic cause of the observed syndrome.
Two affected calves, their parents, and 5576 control cattle genomes.
The affected animals were evaluated clinicopathologically. Paternal half-sibling trio-based whole genome sequencing (WGS) was performed using genomic DNA extracted from the blood of the two affected calves and both dams, and sperm of the common sire.
The cases were presented with a CP Veau II, permanent recumbency, strabismus, tachycardia, and tachypnea. Echocardiographic findings were consistent with tetralogy of Fallot associated with patent foramen ovale (pentalogy of Fallot). Necropsy examination identified hydrocephalus in addition to CP and confirmed the clinical diagnosis of pentalogy of Fallot. The calves were diagnosed with a complex syndromic form of CP with pentalogy of Fallot and hydrocephalus. Analysis of the breeding data showed that 19/45 recorded offspring of the sire were not viable. Genetic analysis identified a missense variant in WDR33 that was heterozygous in both analyzed cases and in an estimated 40% of the paternal gametes of the mosaic founder, but absent in both dams and controls.
This study alerts veterinarians and breeders to the potential occurrence of dominant de novo mutations in cattle and emphasizes that, in herds using a natural service sire, the consequences of an asymptomatic germline mosaic can be important.
腭裂（CP）是一种以腭部开口为特征的先天性缺陷。鉴定出两头患有包括腭裂在内的复杂综合征的杂交父系半同胞。
假设/目标：描述疾病表型并评估所观察到的综合征的遗传原因。
两头患病犊牛、它们的父母以及5576个对照牛基因组。
对患病动物进行临床病理评估。使用从两头患病犊牛及其母亲的血液以及共同父亲的精子中提取的基因组DNA，进行基于父系半同胞三联体的全基因组测序（WGS）。
病例表现为法洛四联症II型腭裂、永久性卧地不起、斜视、心动过速和呼吸急促。超声心动图检查结果与伴有卵圆孔未闭的法洛四联症（法洛五联症）一致。尸检除发现腭裂外还发现脑积水，并证实了法洛五联症的临床诊断。这些犊牛被诊断为患有伴有法洛五联症和脑积水的复杂综合征型腭裂。对繁殖数据的分析表明，该父亲记录的45个后代中有19个无法存活。遗传分析在WDR33中鉴定出一个错义变异，在两个分析病例以及嵌合奠基者估计40%的父系配子中为杂合状态，但在两个母亲和对照中均不存在。
本研究提醒兽医和育种者注意牛群中显性新生突变的潜在发生，并强调在使用自然交配公牛的牛群中，无症状生殖系嵌合的后果可能很重要。
