Expanding the ABCA2-associated neurodevelopmental phenotype
Kaisa T Oja1, Karit Reinson1, Mihkel Ilisson1
1Genetics and Personalized Medicine Clinic, Tartu University Hospital, 50406 Tartu, Estonia; Department of Genetics and Personalized Medicine, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia.
HGG Advances
|June 26, 2026
Summary
This study investigates ATP-binding cassette subfamily A member 2 (ABCA2) gene variants in 17 individuals. Four ABCA2 variants showed impaired transporter function, suggesting a role in disease, but further research is needed.
Area of Science:
- Genetics
- Molecular Biology
- Biochemistry
Background:
- The ATP-binding cassette subfamily A member 2 (ABCA2) gene encodes a transporter protein.
- Biallelic loss-of-function variants in ABCA2 are linked to intellectual disability.
Purpose of the Study:
- To define the phenotypic spectrum of individuals with monoallelic (MV) or biallelic (BV) ABCA2 variants.
- To investigate the functional impact of specific ABCA2 variants.
Main Methods:
- Clinical data collection via questionnaires and literature review.
- Homology modeling for ABCA2 protein structure.
- Untargeted plasma metabolomics.
- Cell viability assays using a docetaxel toxicity model with wild-type and variant ABCA2.
Main Results:
- Seventeen individuals with candidate ABCA2 variants (7 MV, 10 BV) were identified.
- Protein modeling indicated significant impact for 8 of 13 variants.
- Wild-type ABCA2 expression reduced docetaxel-induced cell death, while four variants (p.Asp615Glu, p.Phe754Ser, p.Ile786del, p.Arg926Trp) did not, suggesting loss of function.
- Metabolomics showed a trend toward lower polyunsaturated acylcarnitines in samples from individuals with ABCA2 variants.
Conclusions:
- This study characterizes 17 individuals with candidate ABCA2 variants.
- Four specific ABCA2 variants exhibit altered transporter function.
- Further investigation is required to elucidate the pathomechanism and clinical significance of ABCA2 variants.
