摘要目的 探讨先天性心脏病(CHD)患儿Cited2基因编码链的突变情况.方法 收集120例非同源多种种类的特发性CHD患儿和100例健康儿童血液样本进行DNA抽取、目的 基因聚合酶链反应及测序,并与GeneBank进行比较以识别基因突变,对伴有突变者行家系调查,并用ClustalW软件分析突变氨基酸的保守性.结果在4例CHD患儿发现3个新的Cited2编码链突变,首次在1例镜面右位心伴法洛四联症、1例主动脉瓣狭窄患儿各自发现1个新的点突变(c.550G＞A;c.574A＞G),首次在1例室间隔缺损伴房间隔缺损及1例主动脉瓣狭窄伴肺动脉瓣狭窄患儿发现相同的缺失突变(c.573-578de16),这3种突变均导致了相应蛋白质的结构改变(P.Gly184Ser;p.Serl92Gly;P.Ser192fs),这些突变均未在对照组发现.结论在不同类型的CHD患儿中发现了新的Cited2基因突变,丝氨酸-甘氨酸富含区(SGJ)是突变的热点区域,这些突变可能是导致人类CHD发生的原因之一.

abstractsObjective To explore mutation of Cited2 gene coding strand in Chinese patients with congenital heart disease(CHD).Methods DNA was extracted from the blood samples of 120 nonhomologous and various CHD patients and 100 healthy children.The sequence of coding regions of Cited2 was amplified by PCR and compared to those in the GeneBank after sequencing to identify the mutations.The family of the samples who have Cited2 mutations were investigated as well.ChistalW software was applied for conservative analysis of the altered amino acids.Results Three new mutations of Cited2 coding strand were found in 4 CHD patients.Two point mutations were first identified respectively in two patients,one patient with mirror image dextrocardia and tetralogy of Fallot(c.550 G＞A),another with aortic stenosis (c.574 A＞G).Apart from this,the same deletion(c.573-578del6)was first detected in another two patients,one with ventricular septal defect and atrial septal defect,the other with aortic stenosis and pulmonary stenosis.All the mutations resulted in the protein changes(p.Gly184Ser;p.Ser192Gly;p.Ser192fs).None of these changes were detected in the control group.Conclusion This study showed that there are 3 brand-new gene mutations as demonstrated by sequencing of Cited2 gene in Chinese CHD patients with a broad phenotype spectrum.Serine-glycine rich junction(SGJ)is considered as the mutation hot spot.Cited2 mutations may be one of the causes of the development of CHD in human.