两个JAG1基因突变相关的双侧多囊性发育不良肾胎儿家系的遗传学分析  

Genetic analysis in 2 pedigrees with bilateral multicystic dysplastic kidney associated with JAG1 mutation

作　　者：杨娟[1] 姚光辉 魏振玲[1] 吴庆华[2] YANG Juan;YAO Guanghui;WEI Zhenling;WU Qinghua(Department of Ultrasound,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Center of Genetics and Prenatal Diagnosis,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052)

机构地区：[1]郑州大学第一附属医院超声科,郑州450052 [2]郑州大学第一附属医院遗传与产前诊断中心,郑州450052

出　　处：《郑州大学学报（医学版）》2024年第3期400-404,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金项目(81701497)。

摘　　要：目的:探讨两个双侧多囊性发育不良肾(MCDK)家系的遗传学病因,为两个家系的遗传咨询及再次妊娠指导提供依据。方法:对两个16+周和18+周胎儿行详细超声检查,发现其双侧肾脏呈多囊性发育不良改变,经遗传咨询后胎儿父母决定终止妊娠。取胎儿皮肤进行全外显子组测序,并取父母外周血,采用PCR和Sanger测序验证基因突变位点。结果:全外显子组测序提示家系1胎儿携带JAG1基因c.2078_2079delGT(p.Cys693fs)杂合突变,该突变来自母亲;家系2胎儿携带c.3548_3552delAGAAG(p.Glu1183fs)杂合突变,该突变来源于母亲。结合超声表现及家族史等,这两个双侧MCDK家系的病因为JAG1基因突变相关的Alagille综合征。结论:两个双侧MCDK家系最终确诊为Alagille综合征。Aim:To clarify the genetic etiology in 2 pedigrees with bilateral multicystic dysplastic kidney(MCDK)and to provide genetic counselling for further pregnancy.Methods:Two fetuses of gestational age 16+weeks and 18+weeks were detected by ultrasound examination,and found manifestation of bilateral MCDK.The parents determined to terminate the pregnancy after genetic counselling.Whole exome sequencing was performed by using the skin tissue collected from the fetuses.PCR and Sanger sequencing were used to confirm the results by using the skin samples of fetuses and blood samples of the parents.Results:The fetus in pedigree 1 carried a frameshift mutation of JAG1 gene c.2078_2079delGT(p.Cys693fs),inherited from the mother.The fetus in pedigree 2 carried a frameshift mutation of JAG1 gene c.3548_3552delAGAAG(p.Glu1183fs)derived from the mother.Combined with the ultrasound manifestations and family histories,the fetuses with bilateral MCDK in these 2 pedigrees were diagnosed as Alagille syndrome(ALGS).Conclusion:The genetic etiology of the fetuses in these 2 pedigrees with bilateral MCDK was confirmed as ALGS.

关 键 词：双侧多囊性发育不良肾 JAG1 ALAGILLE综合征 产前诊断 

分 类 号：R692[医药卫生—泌尿科学]