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Posted June 2nd, 2016 by Hilary Vernon & filed under New IEM, Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

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Metodiev and colleagues (AJHG, 98(5), p993–1000, 5 May 2016) recently reported a new mitochondrial disorder of mt-tRNA processing. Pathogenic variants were found in in TRMT10C in 2 unrelated probands via whole exome sequencing protein. Clinical features of the probands included neonatal lactic acidosis, hypotonia, feeding difficulties, deafness, and early death from respiratory failure.

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TRMT10C encodes mitochondrial RNase P (MRPP1). MRPP1, MRPP2 and MRPP3 form the mitochondrial ribonuclease P complex, which is responsible for cleaving the 5? ends of mt-tRNAs from polycistronic precursor transcripts. Functional analysis form proband fibroblasts shows increased mt-tRNA precursors, confirming dysfunctional tRNA processing.

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The clinical presentation of these two probands is very reminiscent of common mitochondrial disorders, and my first inclination in making a genetic diagnosis for similarly presenting patients would likely be to send mtDNA and a limited panel of known mitochondrial genes. With this recent publication, I am once again reminded of the diagnostic limitations of using panels of known mitochondrial genes to diagnosing patients with suspected mitochondrial disease.

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Hilary Vernon, MD PhD