Distinguishing syndromic and nonsyndromic cleft palate through analysis of protein-altering de novo variants in 818 trios.

ABSTRACT: De novo variants (DNs) are sporadically occurring variants found in an offspring but absent in both parents. DNs most commonly arise in the germline and are not under selective pressure; therefore, they may be enriched for disease-causing alleles. In fact, DNs have been implicated in multiple rare genetic disorders. Cleft palate (CP) is a craniofacial congenital anomaly occurring in ∼1 in 1,700 live births. Genome-wide association studies have found fewer than a dozen CP-specific loci, while exome and targeted sequencing studies in family-based and case-control cohorts often lack statistical power to conclusively identify causal variants. We therefore hypothesized that CP probands would be enriched for protein-altering DNs, which may explain the relative dearth in discovery. A complicating

SUBMITTER: Robinson KR 

PROVIDER: S-EPMC12808955 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature