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RRM2B encodes the p53-inducible ribonucleotide reductase small subunit p53R2, essential for mitochondrial DNA (mtDNA) maintenance. Autosomal recessive RRM2B mutations have been described in chronic progressive external ophthalmoplegia (PEO), a core feature of Kearns-Sayre syndrome (PMID:27625884). In Kearns-Sayre syndrome, spontaneous mtDNA deletions of 1.3–8.0 kb affecting oxidative phosphorylation and tRNA genes implicate nuclear maintenance genes including RRM2B (PMID:27625884). However, no case-level RRM2B variants have been reported in clinically confirmed Kearns-Sayre syndrome cohorts, and segregation data are absent. Functional cellular studies demonstrate that loss of p53R2 impairs mtDNA content and mitochondrial function, consistent with a mechanism for mtDNA deletion syndromes. The current association is limited by lack of direct variant–phenotype correlation in Kearns-Sayre syndrome. Key take-home: RRM2B variants are mechanistically plausible contributors to mtDNA deletion–mediated ophthalmoplegia but require dedicated case studies in Kearns-Sayre syndrome.
Gene–Disease AssociationLimitedRRM2B is listed among nuclear genes with PEO-associated mtDNA deletions in Kearns-Sayre syndrome but no case-level variant evidence in KSS patients Genetic EvidenceLimitedNo specific RRM2B variants reported in KSS cohorts; only general PEO data available Functional EvidenceLimitedCellular loss-of-function studies show p53R2 role in mtDNA maintenance but no KSS-specific functional models |