Molecular characteristics
PUS3 (Pseudouridylate Synthase 3) gene is located at 11q24.2 and encodes a protein of the TruA/Pus3 family of pseudouridylases, which isomerizes uracil to pseudouridine at positions 38 and 39 in the anticodon stem and loop of tRNA.
Mutations and pathophysiology
Pseudouridine stabilizes base stacking in oligonucleotides and possesses an additional free NH group allowing for additional hydrogen bonding with other molecules, which allows for increased stability of RNA. PUS3 mutations cause decreased levels of pseudouridine in tRNA.
The following is a selected example of a pathogenic variant in PUS3:
Shaheen et al. (2016) reported a homozygous truncating mutation in PUS3 (NM_031307.3: c.1303C>T: p.(Arg435*)). The affected patients came from a consanguineous Saudi family and displayed the phenotypical features of the disease.