<i>RRM2B</i> mutations are frequent in familial PEO with multiple mtDNA deletions

Abstract

Disorders of mitochondrial DNA (mtDNA) maintenance leading to multiple mtDNA deletions are a significant cause of inherited neurologic disease in adults, but the underlying nuclear gene defects remain elusive in many patients. Following the recent description of a truncating mutation in the RRM2B gene-encoding the small subunit, p53R2, of the p53-inducible ribonucleotide reductase protein-in 2 families with autosomal-dominant progressive external ophthalmoplegia (adPEO), 1 we determined the frequency of RRM2B mutations in a large cohort of patients with PEO and multiple mtDNA deletions in muscle in whom mutations in all known candidate genes (e.g., POLG, POLG2, SLC25A4, and PEO1) had been excluded. 2