Specific combinations of biallelic <i>POLR3A</i> variants cause Wiedemann-Rautenstrauch syndrome

Abstract

Biallelic mutations in <i>POLR3A</i>, which encodes for the largest subunit of the DNA-dependent RNA polymerase III, underlie WRS. No isolated functional sites in POLR3A explain the phenotype variability in POLR3A-related disorders. We suggest that specific combinations of compound heterozygous variants must be present to cause the WRS phenotype. Our findings expand the molecular mechanisms contributing to progeroid disorders.