Disruption of PIKFYVE causes congenital cataract in human and zebrafish.

ABSTRACT: Congenital cataract, an ocular disease predominantly occurring within the first decade of life, is one of the leading causes of blindness in children. However, the molecular mechanisms underlying the pathogenesis of congenital cataract remain incompletely defined. Through whole-exome sequencing of a Chinese family with congenital cataract, we identified a potential pathological variant (p.G1943E) in PIKFYVE, which is located in the PIP kinase domain of the PIKFYVE protein. We demonstrated that heterozygous/homozygous disruption of PIKFYVE kinase domain, instead of overexpression of PIKFYVE^G1943E in zebrafish mimicked the cataract defect in human patients, suggesting that haploinsufficiency, rather than dominant-negative inhibition of PIKFYVE activity caused the dis

SUBMITTER: Mei S 

PROVIDER: S-EPMC8758139 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature