   2.7.7.72 | medicine |
the clinical phenotypes associated with TRNT1 mutations are largely due to impaired mitochondrial translation, resulting from defective CCA addition to mitochondrial tRNASer(AGY), and the severity of this biochemical phenotype determines the severity and tissue distribution of clinical features. TRNT1 mutations A148V and.D128G/Y173F are identified in two unrelated subjects with different clinical features. The first presented with acute lactic acidosis at 3 weeks of age and developed severe developmental delay, hypotonia, microcephaly, seizures, progressive cortical atrophy, neurosensorial deafness, sideroblastic anemia and renal Fanconi syndrome, dying at 21 months. The second presented at 3.5 years with gait ataxia, dysarthria, gross motor regression, hypotonia, ptosis and ophthalmoplegia and had abnormal signals in brainstem and dentate nucleus. In subject 1, muscle biopsy showed combined oxidative phosphorylation defects, but there was no oxidative phosphorylation deficiency in fibroblasts from either subject, despite a 10fold reduction in TRNT1 protein levels in fibroblasts of the first subject. In normal controls, TRNT1 protein levels are 10fold lower in muscle than in fibroblasts |
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