PDF(Pubmed)
Abstract：
Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder. Several male patients with OTCD suffer from severe hyperammonemic crisis in the neonatal period, whereas others develop late-onset manifestations, including hyperammonemic coma. Females with heterozygous pathogenic variants in the OTC gene may develop a variety of clinical manifestations, ranging from asymptomatic conditions to severe hyperammonemic attacks, owing to skewed lyonization. We reported the variants of CPS1, ASS, ASL and OTC detected in the patients with urea cycle disorders through a nation-wide survey in Japan. In this study, we updated the variant data of OTC in Japanese patients and acquired information regarding genetic variants of OTC from patients with OTCD through an extensive literature review. The 523 variants included 386 substitution (330 missense, 53 nonsense, and 3 silent), eight deletion, two duplication, one deletion-insertion, 55 frame shift, two extension, and 69 no category (1 regulatory and 68 splice site error) mutations. We observed a genotype-phenotype relation between the onset time (neonatal onset or late onset), the severity, and genetic mutation in male OTCD patients because the level of deactivation of OTC significantly depends on the pathogenic OTC variants. In conclusion, genetic information about OTC may help to predict long-term outcomes and determine specific treatment strategies, such as liver transplantation, in patients with OTCD.
摘要：
鸟氨酸转碳淀粉酶缺乏症（OTCD）是一种X连锁疾病。几名男性OTCD患者在新生儿期出现严重的高氨血症危象，而其他人则出现迟发性表现，包括高血氨昏迷.在OTC基因中具有杂合子致病变异的雌性可能发展出多种临床表现,从无症状到严重的高氨发作，由于歪斜的抒情。我们报道了CPS1，ASS，通过日本全国范围的调查，在尿素循环障碍患者中检测到ASL和OTC。在这项研究中,我们更新了日本患者的OTC变异数据,并通过广泛的文献综述从OTCD患者获得了有关OTC基因变异的信息.523个变体包括386个取代(330个错义，53废话，和3沉默)，八个删除，两次重复，一个删除插入，55帧移位，两个扩展，69个无类别（1个调节和68个剪接位点错误）突变。我们观察到发病时间（新生儿发病或晚发病）之间的基因型-表型关系，严重程度,男性OTCD患者的基因突变，因为OTC的失活水平显着取决于致病性OTC变异。总之,有关OTC的遗传信息可能有助于预测长期结果并确定特定的治疗策略，比如肝移植,OTCD患者。
