The First Genomic Study in a Romanian Spotted Calf with Ectopia Cordis Thoracalis

Congenital heart defects (CHDs) are defects present at birth that can often lead to perinatal death, or, rarely, can be asymptomatic and detected later in life. Ectopia cordis is a rare type of malformation in which the heart is not located in its normal position. Other congenital abnormalities can be associated with this condition. In this article, we describe a case of ectopia cordis thoracalis with atrial septal defect in association with unilateral renal agenesis in a male Romanian Spotted calf. Clinical examination, dissection, and whole-genome sequencing were performed to describe and identify a possible cause of the abnormalities. Clinical examination revealed the presence of the heart in the thoracic region, subcutaneously, without apparent impairment of major physiological functions. Upon dissection, the external appearance of the heart was normal. However, the internal examination revealed an atrial septal defect measuring 1 cm in diameter in the proximal third of the interatrial septum. The case presented unilateral agenesis of the left kidney. VEP annotation of the joint callset identified 2270 missense variant annotations predicted as deleterious by SIFT and, separately, 12 high-impact start-loss variants by VEP consequence annotation. The OR51F5C and OR8J17 variants were homozygous in the calf. Analyzing genes involved in cardiac and renal development, the following genes—SHH, TBX18, NOTCH1, GATA3, TBX2, FOXC1, and RET had mutations with moderate impact. Mutations in the FOXC1 gene occurred in homozygous states for both the calf and mother genomes, while the RET gene had two mutations in a homozygous state just in the calf genome, and in a heterozygous state in the mother’s genome. One limitation of the present study is the unavailability of the paternal genome for comparative analysis; in addition, maternal genomic profiling did not reveal a contribution to the identified variants. Although the specific pathogenic relevance of the variants detected to the observed phenotype cannot be conclusively established, the findings expand the current genomic knowledge of this rare disorder and provide valuable data for future investigations into its genetic basis.