C-terminal frameshift variants in GPKOW are associated with a multisystemic X-linked disorder.

ABSTRACT:

Purpose

GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.

Methods

We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.

Results

Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented w

SUBMITTER: Mok JW 

PROVIDER: S-EPMC12435177 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature