Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.

ABSTRACT:

Purpose

Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo.

Methods

Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish.

Results

We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressi

SUBMITTER: Lin SJ 

PROVIDER: S-EPMC8956360 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature