Relevance to Autism

Li et al., 2023 determined that a de novo coding-synonymous variant in the PDHA1 gene originally identified in a Japanese ASD proband in Takata et al., 2018 was a non-canonical splicing variant; subsequent functional analysis by minigene splicing assays demonstrated that this variant resulted in deletion of 23 base pairs from exon 14 of this gene. A frameshift variant in the PDHA1 gene had previously been identified in a female ASD proband from the ASPIRE cohort (Callaghan et al., 2019).

Molecular Function

The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 alpha 1 subunit containing the E1 active site, and plays a key role in the function of the PDH complex. Mutations in this gene are associated with pyruvate dehydrogenase E1-alpha deficiency and X-linked Leigh syndrome.

External Links

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