Pathogenic mtDNA mutations causing mitochondrial myopathy: The need for muscle biopsy

Pathogenic mitochondrial tRNA (mt-tRNA) gene mutations represent a prominent cause of primary mitochondrial DNA (mtDNA)-related disease despite accounting for only 5%–10% of the mitochondrial genome.1,2 Although some common mt-tRNA mutations, such as the m.3243A>G mutation, exist, the majority are rare and have been reported in only a small number of cases.3 The MT-TP gene, encoding mt-tRNAPro, is one of the less polymorphic mt-tRNA genes, and only 5 MT-TP mutations have been reported as a cause of mitochondrial muscle disease to date (table e-1 at [Neurology.org/ng][1], P6–10). We report 5 patients with myopathic phenotypes, each harboring different pathogenic mutations in the MT-TP gene, highlighting the importance of MT-TP mutations as a cause of mitochondrial muscle disease and the requirement to study clinically relevant tissue. Acknowledgment: The clinical and diagnostic mitochondrial services in both Newcastle upon Tyne and Oxford are funded by the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children. [1]: /lookup/doi/10.1212/NXG.0000000000000082