Variants in the RRM1 gene may underlie a disorder that is caused by defective processes of mitochondrial DNA (mtDNA) replication and repair. The protein encoded by RRM1, ribonucleotide reductase catalytic subunit M1, forms an essential regulatory part of ribonucleotide reductase. This enzyme catalyzes the production of deoxyribonucleotides – the units that are needed by the organism for DNA synthesis and repair.

An international network of researchers identified autosomal dominant as well as autosomal recessive disease-causing RRM1 variants in five patients from four families. Their patients showed a clinical presentation of a mitochondrial DNA depletion syndrome (MDDS), with ptosis (drooping eyelid) and ophthalmoplegia (eye muscle weakness), additional manifestations and multiple mtDNA deletions in muscle. Further cellular experiments and biochemical investigations performed in the study suggest that the decreased level of mtDNA present in the patients’ cells is caused by an impaired nucleotide synthesis due to the loss of RRM1 protein.

The results of the study were published in the Journal of Clinical Investigation.