TRMT5 – combined oxidative phosphorylation deficiency 26

This report documents a limited gene-disease association between TRMT5 and combined oxidative phosphorylation deficiency 26. A single family proband was identified with compound heterozygous variants in TRMT5, including the coding variant c.1481C>T (p.Thr494Met), supporting an autosomal recessive inheritance pattern. The proband presented with key features such as dyspnea, gastrointestinal dysmotility, and exercise intolerance. Genetic analysis confirmed that the patient inherited one allele from the mother and two different variants from the father, with genetic segregation consistent with the disorder (PMID:35109800).

Functional studies further support the pathogenic role of TRMT5 by demonstrating its critical involvement in mitochondrial tRNA modification and translation. Although these assays—such as methylation activity studies and assessments of mitochondrial function—were carried out in contexts that differ slightly from COXPD26 clinical presentations, they strongly suggest a mechanistic link between TRMT5 dysfunction and impaired oxidative phosphorylation (PMID:33398350). Overall, while direct clinical evidence remains limited to a single family, the converging genetic and functional data underscore a potential causal association. Key take‑home: Even limited clinical findings combined with robust functional data can inform diagnostic decision‑making and future clinical investigations.

References

• BMC Pediatrics • 2022 • Novel heterozygous compound TRMT5 mutations associated with combined oxidative phosphorylation deficiency 26 in a Chinese family: a case report PMID:35109800
• Nucleic Acids Research • 2021 • A deafness-associated tRNA mutation caused pleiotropic effects on the m1G37 modification, processing, stability and aminoacylation of tRNAIle and mitochondrial translation PMID:33398350

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