Quantitative determination of SLC2A1 variant functional effects in GLUT1 deficiency syndrome.

ABSTRACT:

Objective

The goal of this study is to demonstrate the utility of a growth assay to quantify the functional impact of single nucleotide variants (SNVs) in SLC2A1, the gene responsible for Glut1DS.

Methods

The functional impact of 40 SNVs in SLC2A1 was quantitatively determined in HAP1 cells in which SLC2A1 is required for growth. Donor libraries were introduced into the endogenous SLC2A1 gene in HAP1-Lig4KO cells using CRISPR/Cas9. Cell populations were harvested and sequenced to quantify the effect of variants on growth and generate a functional score. Quantitative functional scores were compared to 3-OMG uptake, SLC2A1 cell surface expression, CADD score, and clinical data, including CSF/blood glucose ratio.

Results

Nonsense variants (N = 3) were reduced in cell cul

SUBMITTER: Tayebi N 

PROVIDER: S-EPMC10187726 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature