Clinicopathological and Genomic Characterization of a Simmental Calf with Generalized Bovine Juvenile Angiomatosis

• Published in: Animals (Basel) Vol. 11; no. 3; p. 624
• Main Authors: Jacinto, Joana G P, Häfliger, Irene M, Borel, Nicole, Zanolari, Patrik, Drögemüller, Cord, Veiga, Inês M B
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.02.2021; MDPI
• Subjects: Abdominal wall; Angiomatosis; Anomalies; Antibodies; Antigens; bovine juvenile angiomatosis; Calves; Cattle; Cavities; CD31 antigen; Chromosomes; Congenital defects; Diaphragm; Diaphragm wall; Etiology; Genes; Genomes; Genotype & phenotype; Hemorrhage; Life span; Mediastinum; Mesentery; Mutation; Nodules; Pericardium; Phenotypes; Polymers; precision medicine; rare diseases; Skin; Stroma; Thorax; Tumors; vascular hamartoma; vascular malformation; Veterinary medicine; Vimentin; Viscera; Von Willebrand factor; Whole genome sequencing; United States > US; Switzerland; rare diseases; whole-genome sequencing; precision medicine; vascular hamartoma; cattle; vascular malformation; bovine juvenile angiomatosis
• ISSN: 2076-2615; 2076-2615
• DOI: 10.3390/ani11030624

Bovine juvenile angiomatosis (BJA) comprises a group of single or multiple proliferative vascular anomalies in the skin and viscera of affected calves. The purpose of this study was to characterize the clinicopathological phenotype of a 1.5-month-old Simmental calf with multiple cutaneous, subcutaneous, and visceral vascular hamartomas, which were compatible with a generalized form of BJA, and to identify genetic cause for this phenotype by whole-genome sequencing (WGS). The calf was referred to the clinics as a result of its failure to thrive and the presence of multiple cutaneous and subcutaneous nodules, some of which bled abundantly following spontaneous rupture. Gross pathology revealed similar lesions at the inner thoracic wall, diaphragm, mediastinum, pericardium, inner abdominal wall, and mesentery. Histologically, variably sized cavities lined by a single layer of plump cells and supported by a loose stroma with occasional acute hemorrhage were observed. Determined by immunochemistry, the plump cells lining the cavities displayed a strong cytoplasmic signal for PECAM-1, von Willebrand factor, and vimentin. WGS revealed six private protein-changing variants affecting different genes present in the calf and absent in more than 4500 control genomes. Assuming a spontaneous de novo mutation event, one of the identified variants found in the and genes may represent a possible candidate pathogenic variant for this rare form of vascular malformation.