摘要
目的:探讨胎儿先天性肾脏及泌尿道异常(CAKUT)与染色体非整倍体及拷贝数变异(CNVs)之间的相关性。方法:回顾分析2015年1月至2022年12月在南方医科大学南方医院妇产科产前诊断与遗传病诊断中心行介入性产前诊断的546例胎儿CAKUT病例资料,根据超声特征分为孤立性CAKUT组、CAKUT合并超声软指标异常组及CAKUT合并肾外系统畸形组,对遗传学检测结果与产前超声表型进行相关性分析。结果:(1)546例中胎儿染色体非整倍体检出率为6.3%(34/539),CNVs检出率为5.6%(27/478)。孤立性CAKUT组、CAKUT合并超声软指标异常组及CAKUT合并肾外系统畸形组组间非整倍体检出率比较,差异有统计学意义(P<0.001),孤立性CAKUT组与CAKUT合并肾外系统畸形组CNVs检出率差异有统计学意义(P=0.013)。(2)34例非整倍体胎儿包括13-三体(8/34)、18-三体(2/34)及21-三体综合征(18/34)、Turner综合征(1/34)和嵌合体及易位型非整倍体(6/34)。非整倍体胎儿超声表型前三位依次为肾积水(24/34)、肾脏回声增强(5/34)及多囊性肾发育不良(MCDK)(3/34)。存在肾积水及肾脏回声增强胎儿的非整倍体检出率较高,分别为7.6%(24/316)、10.9%(5/46)。(3)CAKUT胎儿中检出致病(P)CNVs或可能致病性(LP)CNVs共27例(5.6%,27/478),主要发生于17q12(14.8%,4/27)、22q11.21(7.4%,2/27)、22q13.31(7.4%,2/43)、Xp22.31(7.4%,2/27)及5p15.33(7.4%,2/27)区域。CNVs检出率位于前四位的胎儿CAKUT表型(被检测例数>20)为肾脏回声增强(15.9%,7/44)、肾脏体积偏小(15.2%,5/33)、输尿管扩张(11.8%,4/34)及MCDK(8.9%,7/79)。结论:孤立性CAKUT、CAKUT合并超声软指标异常及CAKUT合并肾外系统畸形的胎儿发生染色体非整倍体的风险依次升高。合并肾外系统畸形较孤立性CAKUT胎儿发生CNVs的风险增加。当产前超声提示胎儿肾脏回声增强、MCDK、肾积水、胎儿肾脏体积偏小等表型时,均应提供遗传咨询及介入性产前诊断行染色体核型分析及拷贝数变异检测明确病因。
Objective:To investigate the correlation between fetal congenital anomalies of the kidney and urinary tract(CAKUT)and chromosome aneuploidy and copy number variations(CNVs).Methods:From January 2015 to December 2022,546 cases of CAKUT fetus in Department of Obstetrics and Gynecology of Nanfang Hospital were reviewed,and they were divided into isolated CAKUT group,CAKUT group with abnormal ultrasonic soft index and CAKUT group with extrarenal system malformation,and the correlation between results of genetic test and prenatal ultrasonic phenotype was analyzed.Results:(1)In 546 cases,the detection rate of chromosome aneuploidy was 6.3%(34/539),and the detection rate of CNVs was 5.6%(27/478).There were significant differences among the three groups(P<0.001).There was a statistical difference in the detection rate of CNVs between isolated CAKUT group and CAKUT group with extrarenal system malformation(P=0.013).(2)The 34 cases of aneuploidy included 13-trisomy(8/34),18-trisomy(2/34)a,21-trisomy(18/34),Turner syndrome(1/34)and chimera and translocation aneuploidy(6/34).The first three phenotypes of 34 cases were hydronephrosis(24/34),renal echo enhancement(5/34)and multicystic dysplastic kidney(MCDK)(3/34).The detection rate of aneuploidy in fetus with hydronephrosis and enhanced renal echo was 7.6%(24/316)and 10.9%(5/46)respectively.(3)There were 27 cases(5.6%,27/478)of pathogenic(P)or likely pathogenic(LP)CNVs,CNVs of CAKUT fetuses mainly occurs in 17q12(14.8%,4/27))、22q11.21(7.4%,2/27)、22q13.31(7.4%,2/43)、Xp22.31(7.4%,2/27)and 5p15.33(7.4%,2/27).The top four fetal CAKUT phenotypes with the detection rate of CNVs(number of detected cases>20)were enhanced renal echo(15.9%,7/44),renal hypoplasia(15.2%,5/33),ureteral dilation(11.8%,4/34),and MCDK(8.9%,7/79).Conclusion:The risk of fetus with chromosome aneuploidy in isolated CAKUT,CAKUT with abnormal ultrasound soft indexs and CAKUT with abnormal extrarenal system increases in turn.The risk of CNVs associated with extrarenal system malformation is higher than that of isolated CAKUT fetus.When prenatal ultrasound indicates fetal kidney echo enhancement,MCDK,hydronephrosis and renal agenesis,genetic counseling and interventional prenatal diagnosis should be provided for chromosome karyotype analysis and copy number variation detection to clarify the cause.
作者
唐丽君
刘思平
刘慧冰
裘毓雯
秦霞
贾蓓
Tang Lijun;Liu Siping;Liu Huibing(The Center of Prenatal and Hereditary Disease Diagnosis,Department of Obstetrics and Gynecology,Nanfang Hospital,Southern Medical University,Guangzhou 510515)
出处
《现代妇产科进展》
北大核心
2023年第11期810-815,共6页
Progress in Obstetrics and Gynecology
基金
广东省基础与应用基础研究基金(No:2022A1515220087)
南方医科大学南方医院院长基金(No:2020B015)
广东省重点领域研发计划项目(No:2019B020227001)。
关键词
胎儿
先天性肾脏及泌尿道异常
染色体非整倍体
拷贝数变异
Fetus
Congenital anomalies of the kidney and urinary tract
Chromosome aneuploidy
Copy number variations
