摘要
目的总结胎儿期肾囊性病的产前遗传学诊断情况,探索先天性囊性肾病产前遗传学诊断的临床可行性及意义。方法纳入2017年6月至2019年9月在河南省人民医院诊断为先天性囊性肾病的25例胎儿。经羊膜腔穿刺术抽取羊水标本,17例仅进行了染色体微阵列分析(chromosome microarray analysis,CMA)检查,其他8例同时进行了CMA检查及染色体G显带核型分析,其中6例CMA检查及染色体核型检查阴性结果孕妇接受了临床全外显子组测序(whole exome sequencing,WES)分析。结果25例胎儿中,CMA发现致病性拷贝数变异(pathogenic copy number variantion,pCNV)4例,其中17q12染色体微缺失2例,10p15.1p14染色体微缺失1例,4q21.28q22.1染色体微缺失(含PKD2基因)1例,总体pCNV的检出率约为16.0%(4/25)。8例染色体核型分析均未见异常。进行临床全外显子组测序的6例胎儿中,1例发现NPHS1基因c.1440+1 G>A剪切点杂合突变和c.925G>T无义杂合突变,诊断为芬兰型先天性肾病综合征;1例发现PKD1基因c.6878C>T错义杂合突变,诊断为常染色体显性遗传多囊肾;4例未发现明确致病突变。结论CMA和临床全外显子组测序为代表的二代测序技术是先天性肾囊性疾病精确诊断的有效工具。遗传学诊断有助于明确病因,为部分先天性肾囊性病患儿的预后评估、治疗和家庭遗传咨询等提供依据。
Objective To summarize the diagnosis features of the prenatal genetic diagnosis of fetal renal cystic disease and to explore the clinical feasibility and significance of prenatal genetic diagnosis of congenital cystic nephrosis.Methods A total of 25 fetuses with congenital renal cystic disease were examined via invasive prenatal diagnosis in Henan Provincial People's Hospital from June 2017 to September 2019.Amniotic fluid samples were extracted by amniocentesis.Chromosomal microarray analysis(CMA)were performed in 17 cases.In addition to CMA,the other 8 cases were analyzed by G-band karyotype.Whole exome sequencing(WES)was performed in 6 cases which got normal results by CMA and karyotype,and highly suspected as hereditary disease.Results Of the 25 fetuses assessed,4 cases(16.0%)pathogenic copy number variation(pCNV)were found,including 2 cases of 17q12 deletion,1 case of 10p15.1p14 deletion and 1 case of 4q21.28q22.1 deletion(including PKD2 gene).There were 8 cases without chromosome abnormality by karyotype analysis.Six clinical WES analysis found NPHS1 gene c.1440+1 G>A and c.925G>T mutations were related to Finnish type congenital nephrotic syndrome in 1 case,PKD1 gene c.6878C>T mutation was related to autosomal dominant polycystic kidney disease(ADPKD)in 1 case,and there was no definitive mutation in 4 cases.Conclusions CMA and next generation sequencing are powerful tools for accurate diagnosis,treatment and genetic counseling of fetal congenital renal cystic diseases.For congenital cystic nephropathy,genetic detection is helpful to clarify the etiology,and provide more exactly informations for prognosis evaluation,treatment and family genetic counseling.
作者
侯巧芳
王莉
吴东
杨科
楚艳
王睿丽
马旭
廖世秀
Hou Qiaofang;Wang Li;Wu Dong;Yang Ke;Chu Yan;Wang Ruili;Ma Xu;Liao Shixiu(Institute of Medical Genetics,Henan Provincial People's Hospital,Zhengzhou 450003,China;Henan Key Laboratory of Functional Genomics,Henan Provincial People's Hospital,Zhengzhou 450003,China;Center for Reproductive Medicine,Chinese People's Liberation Army Joint Logistics Support Force No.988,Zhengzhou 450001,China;Department of Ultrasound,Henan Provincial People's Hospital,Zhengzhou 450003,China;Department of Nephrology,Henan Provincial People's Hospital,Zhengzhou 450003,China)
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2021年第3期168-175,共8页
Chinese Journal of Nephrology
基金
河南省医学科技攻关计划项目(201701016)。
