Biallelic loss-of-function variants in CACHD1 cause a novel neurodevelopmental syndrome with facial dysmorphism and multisystem congenital abnormalities.

ABSTRACT:

Purpose

We established the genetic etiology of a syndromic neurodevelopmental condition characterized by variable cognitive impairment, recognizable facial dysmorphism, and a constellation of extra-neurological manifestations.

Methods

We performed phenotypic characterization of 6 participants from 4 unrelated families presenting with a neurodevelopmental syndrome and used exome sequencing to investigate the underlying genetic cause. To probe relevance to the neurodevelopmental phenotype and craniofacial dysmorphism, we established two- and three-dimensional human stem cell-derived neural models and generated a stable cachd1 zebrafish mutant on a transgenic cartilage reporter line.

Results

Affected individuals showed mild cognitive impairment, dysmorphism featuring ocu

SUBMITTER: Scala M 

PROVIDER: S-EPMC11910193 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature