Molecular diagnoses and candidate gene identification in the congenital heart disease cohorts of the 100,000 genomes project.

ABSTRACT: Congenital heart disease (CHD) describes a structural cardiac defect present from birth. A cohort of participants recruited to the 100,000 Genomes Project (100 kGP) with syndromic CHD (286 probands) and familial CHD (262 probands) were identified. "Tiering" following genome sequencing data analysis prioritised variants in gene panels linked to participant phenotype. To improve diagnostic rates in the CHD cohorts, we implemented an agnostic de novo Gene Discovery Pipeline (GDP). We assessed de novo variants (DNV) for unsolved CHD participants following filtering to select variants of interest in OMIM-morbid genes, as well as novel candidate genes. The 100kGP CHD cohorts had low rates of pathogenic diagnoses reported (combined CHD "solved" 5.11% (n = 28/548)). Our GDP provided diagnostic upl

SUBMITTER: Hartill V 

PROVIDER: S-EPMC12185689 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature