Hypospadias and Bilateral Cleft Lip and Jaw in a Crossbred Calf: WGS Sequence

Congenital abnormalities in animals are a major concern for breeders due to increased economic losses, and abnormalities of the cleft lip and jaw and hypospadias, reported in all domesticated species, are among them. In this article, we describe a congenital bilateral cleft lip and jaw, CLJ, in association with campylognathia and with perineal hypospadias in a Piedmontese x Wagyu calf. Clinical examination, histopathology, computed tomography, and whole genome sequencing were performed to describe and identify a possible cause. Clinical examination revealed a bilateral cleft lip and jaw of approximately 4 cm in length and 3 cm in width in the widest part, with computer tomography analyses confirming the bilateral absence of the process nasalis of the incisive bone and the lateral deviation of the processus palatinus toward the left side. The histological examination of the urethra revealed the normal structure, except corpus cavernosa of the penis that had undergone a process of adipose degeneration. Analyzing 559 unique genes associated with CLJ and hypospadias, we identified 13 mutations with a high impact on the following overlapped genes: EGF, IRF6, CCDC8, ACVR1, PHC2, MYBPHL, BMPRIB, BHMT2, MMP14, CDH1, F13A1, ADGRA2, and GSTP1, with few data on the genes ADGRA2, BMPRIB, CDH1, CCDC8, F13A1, MYBPHL, PHC2 and their role in the impairment of embryonic development of the two anatomical regions identified in this case. The whole genome investigation indicates the involvement of multiple genes in the two birth defects in bovine species.