鸟氨酸氨甲酰基转移酶缺陷症三例临床和基因突变分析

Clinical and gene mutation analyses of three patients with ornithine carbamoyltransferase deficiency

目的分析鸟氨酸氨甲酰基转移酶缺陷症（ornithine carbamoyhransferase deficiency,OTCD） 的临床表现、遗传学特点，从基因水平了解OTCD的致病因素，达到基因诊断和遗传咨询的目的。方法应用聚合酶链反应扩增3例OTCD患者的鸟氨酸氨甲酰转移酶 （ornithine carbamoyltransferase, OTC） 基因各个外显子所在片段，并进行直接测序，以检测突变。结果例1在生后6月以呕吐起病，为错义突变T262I，其母亲表型正常，为T262I杂合突变；例2在2岁时以烦躁不安起病，为错义突变R277W，例2父母未行基因检测；例3以嗜睡在新生儿期起病，为错义突变1172M，其母表型正常，为1172M杂合突变。结论基因分析是诊断OTCD有效可行的方法。T262I突变及R277W突变是症状较轻的温和突变，1172M突变是起病年龄早及症状重的突变。对致病基因进行突变检测不仅可以诊断OTCD，而且可以发现无症状的基因携带者，为遗传咨询及产前诊断提供依据。

Objective To analyze the clinical and genetic characteristics of three children with ornithine carbamoyltransferase deficiency（OTCD）, and to provide a practical method for gene diagnosis and genetic counseling of the disease. Methods All exons of the ornithine carbamoyltransferase （OTC） gene were screened by polymerase chain reaction-DNA direct sequencing in the three OTCD patients. Results One patient firstly presented as vomiting at 6 month of age. A missense mutation of T262I was detected. His mother had the same mutation without any clinical symptoms. The second patient presented as restlessness, and had a missense mutation of R277W. Gene analysis of his parents was not available. The third patient presented as neonatal lethargy, harbored a missense mutation of I172M. His mother had the same mutation without any clinical symptoms. Conclusion Gene mutation analysis is a feasible way for diagnosing OTCD. Patients with I172M mutation present symptom early, while those with T262I and R277W mutations manifest symptoms later. Gene mutation analysis will be important for asymptomatic and prenatal diagnosis and genetic counseling.