Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene.

ABSTRACT: Predicting the pathogenicity of biallelic missense variants can be challenging. Here, we use a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes. We follow three missense variants with a complete deficit of homozygosity and find that their pathogenic effect in homozygous state ranges from severe childhood disease to early embryonic lethality. One of these variants is in CPSF3, a gene not previously linked to disease. From a set of clinically sequenced Icelanders, and by sequencing archival samples targeted through the Icelandic genealogy, we find four homozygous carriers. Additionally, we find two homozygous carriers of Mexican descent of another missense varian

SUBMITTER: Arnadottir GA 

PROVIDER: S-EPMC8817032 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature