A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion

This report describes two brothers, both deceased in infancy, with severe depletion of mitochondrial DNA (mtDNA) in muscle tissue. Both had feeding difficulties, failure to thrive, severe muscular hypotonia and lactic acidosis. One of the boys developed a renal proximal tubulopathy. A novel homozygous c.686 G→T missense mutation in the RRM2B gene, encoding the p53-inducible ribonucleotide reductase subunit (p53R2), was identified. This is the third report on mutations in RRM2B associated with severe mtDNA depletion, which further highlights the importance of de novo synthesis of deoxyribonucleotides (dNTPs) for mtDNA maintenance.