Rare variants found in clinical gene panels illuminate the genetic and allelic architecture of orofacial clefting.

ABSTRACT:

Purpose

Orofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls.

Methods

We evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria.

Results

9.04% of cases and 1.02% of controls had "likely pathogenic" variants (P < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft

SUBMITTER: Diaz Perez KK 

PROVIDER: S-EPMC10592535 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature