Homozygous missense variants in YKT6 result in loss of function and are associated with developmental delay, with or without severe infantile liver disease and risk for hepatocellular carcinoma.

ABSTRACT:

Purpose

YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases.

Methods

We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6^KozakGAL4 allele to assess the expression pattern of dYkt6.

Results

Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thr

SUBMITTER: Ma M 

PROVIDER: S-EPMC11335040 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature