Genetics of childhood-onset hypertension

National Human Genome Research Institute

Investigators

Linked publications, trials & patents

Abstract

Our previous publication (Copeland, Wonkam Tingang, et al, 2024) identified rare, likely protein-damaging genetic variants inherited in the SYNE1 gene leading to an increased risk of developing COEH. We continue to look for additional candidate genes through sequencing of international and national cohorts, and molecular and clinical characterization of COEH patients in the NIH clinical center. In parallel, we are leveraging model organisms and cellular studies to validate candidates and better understand the underlying molecular mechanisms of disease. In the current reporting period, we: - Reduced expression of strong candidate genes in smooth muscle vascular cells and assessed cellular morphology and stiffness using atomic force microscopy (collaboration with NIBIB). - Developed protocols for assessing candidate gene proteins and gene expression in patient samples and cellular models - Reported on physiological biomarkers of cardiovascular health in adolescents (Wentzel et al, 2025) - Evaluated in vivo blood pressure in murine models of reduced gene expression and identified a) significantly different blood pressure from wild type models (collaboration with NHLBI) and b) abnormal vessel integrity on histology (collaboration with NCI). - Surveyed the All of Us Project database to validate an enrichment of candidate gene variants among individuals with reported COEH versus population controls - Validated candidates identified in our original Texas cohort using whole genome sequencing of DNA from 187 children from South Africa (Collaboration with the North-West University in South Africa). - Obtained ethical approval for our clinical natural history protocol to identify and recruit COEH individuals from the community. The first four probands from two families have consented to be seen and have been evaluated in the clinical center.