A homozygous synonymous NOP58 variant associated with a novel ribosomopathy

Abdelrazek, I. (2025). A homozygous synonymous NOP58 variant associated with a novel ribosomopathy (Version 1) [DataSet]. GestaltMatcher Database.

Ribosomes, composed of ribosomal proteins and rRNAs, synthesize proteins in all cells. Pre-rRNAs undergo processing and 2’-O-methylation, guided by box C/D snoRNPs, which include a snoRNA and core proteins NOP56, NOP58, SNU13, and fibrillarin. Through trio whole-exome sequencing in a patient with severe neurodevelopmental issues (global delay, microcephaly, seizures, and brain/eye abnormalities) and his healthy parents, we identified a homozygous synonymous NOP58 variant (c.516G>A; p.Leu172=). Functional studies in patient fibroblasts revealed reduced NOP58 protein levels and disrupted nucleolar function, likely impairing box C/D snoRNP biogenesis and contributing to the patient’s neurodevelopmental phenotype.