A new mutation in the mitochondrial tRNAPro gene associated with early-onset neuromuscular phenotype and ragged-red fibers

•By Next-Generation Sequencing, we identified a novel heteroplasmic mutation in the mitochondrial tRNAPro, m.15958A>T.•We present a case of early-onset neuromuscular phenotype with ragged-red and COX negative fibers.•This case confirms the clinical heterogeneity associated with MTTP mutations.

An 11-year-old boy with psychomotor delay, exercise intolerance, ptosis and growth delay had a muscle biopsy showing typical mitochondrial alterations (60% of ragged-red fibers and 90% of cytochrome-c oxidase-deficient fibers). Next-generation sequencing revealed a novel heteroplasmic mutation (m.15958A>T) in the MTTP gene that encodes tRNAPro. The mutation was not present in the accessible non-muscle tissues of the patient's asymptomatic mother. Mutations in the rarely affected MTTP gene are responsible for different clinical presentations. We report the third early-onset case associated with a mutation in this gene. The severity of myopathy is likely related to the high mutation rate (96%) found in the patient's muscle. The clinical heterogeneity associated with MTTP mutations illustrates the value of the next-generation sequencing in routine diagnosis of mitochondrial diseases.