Kearns-Sayre syndrome caused by defective R1/p53R2 assembly

RRM2B is a nuclear gene that encodes p53R2, a protein required for synthesising mitochondrial DNA (mtDNA). Accumulation of multiple mtDNA deletions in muscle and other tissues is a relatively frequent cause of mitochondrial disease in adults. Multiple mtDNA deletions arise because of faulty mtDNA replication, and we now show that 4% of 50 patients seen at our hospital with multiple mtDNA deletions had RRM2B mutations. One patient had Kearns-Sayre syndrome (KSS), which is usually a sporadic disorder; this is the first case to be linked to a nuclear gene defect. Identification of RRM2B mutations in patients with KSS when multiple mtDNA deletions are present is crucial for accurate genetic counselling. We also provide important insight into how RRM2B mutations cause disease by demonstrating impaired assembly of the p53R2 protein using the technique of Blue native gel electrophoresis. (By Dr Robert Pitceathly, http://jmg.bmj.com/content/early/2011/03/04/jmg.2010.088328.abstract?papetoc= )