CAJ | 학술논문

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.
목적 통과분석3례림상의진조안산안갑선기전이매결핍증(ornithine transcarbamylase deficiency,OTCD)신생인혈대사보변화급조안산안갑선기전이매(ornithine transcarbamylase,OTC)기인돌변류형,재기인수평진일보료해OTCD적치병궤리,이기체도분자진단화유전자순적목적.방법 분석3례환인림상특정,응용천련질보대환인진행안기산선기육감보분석,병채집환자외주혈,제취기인조DNA,응용PCR확증OTC기인적전부외현자,대PCR산물진행쌍향측서검측기인돌변.결과 3례환인균위신생인기병,표현위정신반응차,위양곤난,추휵,신생인감염.혈천련질보검측결과균현시과안산농도명현하강.례1 OTC기인검측결과위위우제6외현자적착의돌변Y183C;례2위위우제10외현자적착의돌변V339G;례3위위우제9외현자적착의돌변W332S.결론 대OTC기인서렬분석불부가진단OTCD,동시가사사출무증상휴대자,위유가족사적개체진행산전진단화유전자순제공이론의거.례2화례3적V339G、W332S적량충기인돌변류형재국내외균미견보도,보고적3충돌변균도치신생인기급성기병.
Objective 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.