Whole exome sequencing of 80 cases of sporadic mitral valve prolapse reveals novel disease-associated genes and variants in a Southern Chinese population.

Background: Mitral valve prolapse (MVP) is a common valvular disorder with a complex genetic basis. While familial MVP-related genes have been identified, the genetic determinants of sporadic MVP remain unclear.

Objective: This study aims to identify causative genes associated with sporadic MVP and analyze genotype-phenotype correlations in a southern Chinese population.

Methods: Whole-exome sequencing (WES) was performed on 80 patients with sporadic MVP. Pathogenic variants were screened using population databases and bioinformatic tools. Gene enrichment and genotype-phenotype correlation analyses were conducted.

Results: A total of 145 variants in 104 MVP-associated genes were identified. Five known MVP genes (COL1A2, FLNA, FLNC, TGFB1, TTN) were found in 14 patients. Three novel MVP-related genes (PRDM5, ZNF469, COL11A1) were identified, predominantly in fibroelastic deficiency cases. These patients had younger onset and higher early diastolic peak velocities.

Conclusions: Sporadic MVP exhibits genetic heterogeneity, with pathogenic mutations linked to early-onset disease and left ventricular dilation. Early genetic screening may improve diagnosis and risk assessment.