先天性功能性孤立肾胎儿的遗传学病因:422例分析  

Genetic etiology of fetuses with congenital solitary functioning kidney:analysis of 422 cases

作　　者：陈阳 丁红珂[2] 卢建[2] 朱娟[2] 吕莉娟[2] Chen Yang;Ding Hongke;Lu Jian;Zhu Juan;Lyu Lijuan(Graduate School of Guangzhou Medical University,Guangzhou 511436,China;Medical Genetics Center,Guangdong Women and Children Hospital,Guangzhou 511400,China)

机构地区：[1]广州医科大学研究生院,广州511436 [2]广东省妇幼保健院医学遗传中心,广州511400

出　　处：《中华围产医学杂志》2025年第3期185-193,共9页Chinese Journal of Perinatal Medicine

摘　　要：目的探讨先天性功能性孤立肾(congenital solitary functioning kidney,CSFK)的遗传学病因。方法本研究为回顾性研究,研究对象为2015年1月至2023年2月在广东省妇幼保健院因产前超声提示CSFK而接受介入性产前遗传学诊断的422例胎儿。分析CSFK胎儿各亚型(单侧肾缺如和单侧多囊性肾发育不良)、各组(孤立性和非孤立性CSFK)的G显带核型分析、染色体微阵列分析(chromosomal microarray analysis,CMA)和全外显子组测序(whole exome sequencing,WES)检测结果。采用χ^(2)检验(或Fisher精确概率法)或秩和检验进行统计学分析。结果(1)422例胎儿母亲行介入性产前诊断时年龄为29(18~43)岁,孕周为25(17~34)周。234例接受了核型分析和CMA,63例接受了CMA和WES,7例同时接受了上述3种检测。故核型分析、CMA和WES分别完成了257、406和70例。(2)G显带核型分析的染色体异常检出率为1.6%(4/257)。这4例同时进行CMA检测,1例染色体嵌合胎儿样本未检出异常,3例染色体结构重排胎儿的CMA结果与G显带核型分析结果基本一致。(3)CMA的CNV检出率为8.9%(36/406),其中22例为致病性/可能致病性CNV。22例常见的CNV位点为17q12(5例)、22q11.21(5例)和16p11.2(2例);15例(68.2%)为微缺失综合征。这22例中的19例胎儿母亲选择引产终止妊娠,2例继续妊娠,1例失访。(4)共有241例同时进行了G显带核型分析和CMA检测(包括7例同时进行3种检测者),G显带核型分析和CMA的阳性率分别为1.7%(4/241)和5.8%(14/241)。与G显带核型分析相比,CMA可获得4.1%(10/241)的额外诊断率。(5)70例进行了家系WES检测,26例(37.1%)结果异常,其中致病/可能致病性12例,临床意义未明14例,WES阳性率为17.1%(12/70)。6例检出的基因变异(主要为PKD1和HNF1B基因变异)与胎儿CSFK表型有关,其中5例为常染色体显性遗传,1例为常染色体隐性遗传。在12例WES阳性病例中,杂合变异和复合杂合变异各6例;8例胎儿母亲选择继续�ObjectiveTo explore the genetic etiology of congenital solitary functioning kidney(CSFK).MethodsThis retrospective study included 422 fetuses diagnosed with CSFK by prenatal ultrasound who underwent invasive prenatal genetic testing at Guangdong Women and Children Hospital between January 2015 and February 2023.These CSFK fetuses were classified into different subtypes(unilateral renal agenesis and unilateral multicystic dysplastic kidney)and divided into the isolated group(n=312)and the non-isolated group(n=110)based on whether there were other associated abnormalities.The results of G-banding karyotyping,chromosomal microarray analysis(CMA),and whole-exome sequencing(WES)among fetuses with different subtypes or from different groups were analyzed.Statistical analysis was performed using the Chi-square(or Fisher's exact)test and rank-sum test.Results(1)The median maternal age at the time of invasive prenatal diagnosis was 29 years(range:18-43 years),and the median gestational age was 25 weeks(range:17-34 weeks).Among the 422 cases,234 underwent karyotyping and CMA,63 underwent CMA and WES,and seven underwent all three tests.Therefore,karyotyping,CMA,and WES were completed in 257,406,and 70 cases,respectively.(2)The detection rate of chromosomal abnormality by G-banding karyotyping was 1.6%(4/257).Among these four cases,CMA detected no abnormalities in one case with chromosomal mosaicism,while the CMA results were consistent with G-banding karyotyping in three cases with chromosomal structural rearrangements.(3)CMA results:The CNV detection was 8.9%(36/406),with 22 cases being classified as pathogenic/likely pathogenic CNVs.Common CNV loci included 17q12(five cases),22q11.21(five cases),and 16p11.2(two cases).Fifteen cases(68.2%)were associated with microdeletion syndromes.Nineteen mothers opted for pregnancy termination,two continued the pregnancies,and one was lost to follow-up.(4)Among the 241 cases that underwent both G-banding karyotyping and CMA(including seven cases with all three tests),the positive rates

关 键 词：孤立肾 产前诊断 染色体畸变 回顾性研究 

分 类 号：R714.5[医药卫生—妇产科学]