Phenotypic Correlates of Structural and Functional Protein Impairments Resultant from ALDH5A1 Variants.

ABSTRACT:

Objective

To investigate the genotype-to-protein-to-phenotype correlations of succinic semialdehyde dehydrogenase deficiency (SSADHD), an inherited metabolic disorder of γ-aminobutyric acid catabolism.

Methods

Bioinformatics and in silico mutagenesis analyses of ALDH5A1 variants were performed to evaluate their impact on protein stability, active site and co-factor binding domains, splicing, and homotetramer formation. Protein abnormalities were then correlated with a validated disease-specific clinical severity score and neurological, neuropsychological, biochemical, neuroimaging, and neurophysiological metrics.

Results

A total of 58 individuals (1:1 male/female ratio) were affected by 32 ALDH5A1 pathogenic variants, eight of which were novel. Compared to individuals

SUBMITTER: Latzer IT 

PROVIDER: S-EPMC10371128 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature