Compound heterozygous variants within two conserved sialyltransferase motifs of ST3GAL5 cause GM3 synthase deficiency.

ABSTRACT: GM3 synthase deficiency (GM3SD) is caused by biallelic variants in ST3GAL5. The ganglioside GM3, enriched in neuronal tissues, is a component of lipid rafts and regulates numerous signaling pathways. Affected individuals with GM3SD exhibit global developmental delay, progressive microcephaly, and dyskinetic movements. Hearing loss and altered skin pigmentation are also common. Most of the reported variants in ST3GAL5 are found in motifs conserved across all sialyltransferases within the GT29 family of enzymes. These motifs include motif L and motif S which contain amino acids responsible for substrate binding. These loss-of-function variants cause greatly reduced biosynthesis of GM3 and gangliosides derived from GM3. Here we describe an affected female with typical GM3SD feat

SUBMITTER: Rudy N 

PROVIDER: S-EPMC9981410 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature