Division of Genetics, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 777, Rochester, NY 14623, USA.
Pediatr Nephrol. 2013 Mar;28(3):515-9. doi: 10.1007/s00467-012-2354-y. Epub 2012 Nov 8.
We identified a mitochondrial tRNA mutation (m.586 G > A) in a patient with renal failure and symptoms consistent with a mitochondrial cytopathy. This mutation was of unclear significance due to the absence of consistent reports of linkage to specific disease phenotypes and any data pertaining to its effects on mitochondrial function.
CASE-DIAGNOSIS/TREATMENT: A 16-month-old girl with failure-to-thrive, developmental regression, persistent lactic acidosis, hypotonia, gastrointestinal dysmotility, adrenal insufficiency, and hematologic abnormalities developed hypertension and renal impairment with chronic tubulointerstitial fibrosis, progressing to renal failure with the need for peritoneal dialysis. Evaluation of her muscle and blood led to the identification of a mutation of the mitochondrial tRNA for phenylalanine, m.586 G > A.
The m.586 G > A mutation is pathogenic and a cause of end-stage renal disease in childhood. The mutation interferes with the stability of tRNA(Phe) and affects the translation of mitochondrial proteins and the stability of the electron transport chain.
我们在一名肾衰竭患者中发现了一个线粒体 tRNA 突变（m.586 G > A），其症状与线粒体细胞病变一致。由于缺乏与特定疾病表型相关的一致报道，以及任何关于其对线粒体功能影响的数据，因此该突变的意义尚不清楚。
病例诊断/治疗：一名 16 个月大的女孩因生长发育迟缓、发育倒退、持续性乳酸酸中毒、肌张力低下、胃肠动力障碍、肾上腺功能不全和血液学异常而就诊，后出现高血压和肾功能损害，表现为慢性肾小管间质性纤维化，进展为终末期肾衰竭，需要进行腹膜透析。对其肌肉和血液的评估导致发现了线粒体 tRNA 对苯丙氨酸的突变，m.586 G > A。
m.586 G > A 突变是致病性的，是儿童终末期肾病的病因。该突变干扰 tRNA(Phe)的稳定性，影响线粒体蛋白的翻译和电子传递链的稳定性。
