Seven Additional Patients with SOX17 Related Pulmonary Arterial Hypertension and Review of the Literature

Genes (Basel). 2023 Oct 20;14(10):1965. doi: 10.3390/genes14101965.

Abstract

Pulmonary arterial hypertension (PAH) is an infrequent disorder characterized by high blood pressure in the pulmonary arteries. It may lead to premature death or the requirement for lung and/or heart transplantation. Genetics plays an important and increasing role in the diagnosis of PAH. Here, we report seven additional patients with variants in SOX17 and a review of sixty previously described patients in the literature. Patients described in this study suffered with additional conditions including large septal defects, as described by other groups. Collectively, sixty-seven PAH patients have been reported so far with variants in SOX17, including missense and loss-of-function (LoF) variants. The majority of the loss-of-function variants found in SOX17 were detected in the last exon of the gene. Meanwhile, most missense variants were located within exon one, suggesting a probable tolerated change at the amino terminal part of the protein. In addition, we reported two idiopathic PAH patients presenting with the same variant previously detected in five patients by other studies, suggesting a possible hot spot. Research conducted on PAH associated with congenital heart disease (CHD) indicated that variants in SOX17 might be particularly prevalent in this subgroup, as two out of our seven additional patients presented with CHD. Further research is still necessary to clarify the precise association between the biological pathway of SOX17 and the development of PAH.

Keywords: SOX17; cardiovascular disorders; congenital heart disease; genomic medicine; personalized medicine; pulmonary arterial hypertension; whole exome sequencing.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Familial Primary Pulmonary Hypertension
  • Heart Defects, Congenital*
  • Heart Septal Defects*
  • Humans
  • Pulmonary Arterial Hypertension* / diagnosis
  • Pulmonary Arterial Hypertension* / genetics
  • Pulmonary Artery
  • SOXF Transcription Factors / genetics

Substances

  • SOX17 protein, human
  • SOXF Transcription Factors