摘要目的 通过分析3例临床疑诊鸟氨酸氨甲酰基转移酶缺乏症(ornithine transcarbamylase deficiency,OTCD)新生儿血代谢谱变化及鸟氨酸氨甲酰基转移酶(ornithine transcarbamylase,OTC)基因突变类型,在基因水平进一步了解OTCD的致病机理,以期达到分子诊断和遗传咨询的目的.方法 分析3例患儿临床特征,应用串联质谱对患儿进行氨基酸酰基肉碱谱分析,并采集患者外周血,提取基因组DNA,应用PCR扩增OTC基因的全部外显子,对PCR产物进行双向测序检测基因突变.结果 3例患儿均为新生儿起病,表现为精神反应差,喂养困难,抽搐,新生儿感染.血串联质谱检测结果均显示瓜氨酸浓度明显下降.例1 OTC基因检测结果为位于第6外显子的错义突变Y183C;例2为位于第10外显子的错义突变V339G;例3为位于第9外显子的错义突变W332S.结论 对OTC基因序列分析不仅可诊断OTCD,同时可筛查出无症状携带者,为有家族史的个体进行产前诊断和遗传咨询提供理论依据.例2和例3的V339G、W332S的两种基因突变类型在国内外均未见报道,报告的3种突变均导致新生儿期急性起病.

abstractsObjective To analyze the clinical features,metabolic profiling and gene mutations of patients with ornithine transcarbamylase deficiency (OTCD) and explore the molecular pathogenesis of OTCD in order to provide a solution for molecular diagnostics and genetic counseling.Methods Clinical data of 3 neonates were analyzed.The amino acids level in blood was analyzed with mass spectrum technology.PCR was used to amplify all the 10 exons of OTC gene.The PCR products were directly sequenced to detect the mutations.Results All of the 3 cases had neonatal onset and showed poor reaction,feeding difficulty,convulsion and neonatal infection.Citrulline levels were significantly decreased.Case 1 had a missense mutation of Y183C.Case 2 showed a missense mutation of V339G in exon 10.And a missense mutations of W332S in exon 9 was detected in case 3.Conclusion Analysis of OTC gene sequences can be used for the diagnosis of OTCD and screening of asymptomatic carriers.Mutation analysis is important for prenatal diagnosis of individuals with a positive family history and genetic counseling.The V339G and W332S mutations have been discovered for the first time.Patients with such mutations may have onset of the disease during neonatal period.