A novel polyribonucleotide nucleotidyltransferase 1 (PNPT1) gene variant potentially associated with combined oxidative phosphorylation deficiency 13: case report and literature review.

Background: Combined oxidative phosphorylation deficiency 13 (COXPD13) results from mutations in the mitochondrial polyribonucleotide nucleotidyltransferase 1 (PNPT1) gene. However, none of COXPD13 is reported in China. This study presents the clinical and molecular genetic features of an infant of Chinese descent identified with a novel PNPT1 mutation, which may be associated with COXPD13.

Case description: Here, we presented a case of a Chinese boy exhibiting multiple organ damage, white matter changes, epilepsy, abnormalities in muscle tone and strength, global developmental delay, growth retardation, and visual and auditory impairment. The patient also showed elevated lactate levels in the plasma. Furthermore, whole-exome sequencing (WES) revealed a homozygous mutation, c.1033A>G (p.K345E), in the PNPT1 gene. Self-optimized prediction method (SOPMA) and AlphaFold modeling, along with missense 3-dimensional (3D) prediction, indicated that this variant negatively impacted both the secondary and tertiary structures of the PNPT1 protein. The PNPT1 variant may alter the surface electrostatic potential at position 345 from electropositive to electronegative. Additionally, mutant cutoff scanning matrix (mCSM), and daughters, dudes, mothers, and others fighting cancer together (DUET) predicted that the variant disrupted the stability of the protein structure.

Conclusions: The novel PNPT1 gene variant, c.1033A>G (p.K345E), is predicted to disrupt the secondary and tertiary structures of the PNPT1 protein, impairing its normal function. This disruption may lead to mitochondrial RNA processing defects, contributing to the development of COXPD13.