产前诊断胎儿泌尿系统畸形与染色体1q21．1微缺失  

Prenatal diagnosis of fetal urinary abnormalities and microdeletion on chromosome lq21.1

作　　者：符芳[1] 黄泳华[2] 廖灿[1] 李茹[1] 冯穗华[2] 麦巧娇[2] 李卫凯[2] 

机构地区：[1]广州医学院附属广州市妇女儿童医疗中心产前诊断中心,510623 [2]广东省江门市中心医院妇产科

出　　处：《中华医学遗传学杂志》2012年第5期505-509,共5页Chinese Journal of Medical Genetics

基　　金：十一五国家科技支撑计划项目（2006BA105A09）;广东省自然科学基金（9151018005000001）;广州市卫生局重点项目（201102）

摘　　要：目的应用微阵列比较基因组杂交技术探讨胎儿先天性泌尿系统畸形的遗传学病因。方法选取32例经产前超声检查提示发生不同程度泌尿系统畸形并且常规G显带核型分析方法未发现异常的胎儿病例及其父母的DNA，按照标准的Affymetri xcytogenetic2．7M芯片的操作手册进行杂交、洗涤及全基因组扫描，应用配套的CHAS软件分析结果。结果微阵列比较基因组杂交技术检测发现9例胎儿基因组发生了不平衡的拷贝数变异（copy number variations，CNVs），检出率为28％。其中4例CNVs遗传自亲代（12．5％）；2例CNVs在相关数据库中提示在正常人基因组中存在（6％）；3例是新发的致病性CNVs（9％），并且这3例胎儿样本均发生了染色体1q21．1微缺失和微重复，异常片段内包含与泌尿生殖系统功能密切相关的PDZK1基因。结论先天性泌尿系统畸形胎儿基因组发生不平衡畸变的几率约为28％，其中致病性的基因组不平衡异常约占9％。染色体lq21．1区带DNA拷贝数改变是导致先天性泌尿系统畸形的病因之一，其致病机制可能与PDZK1基因的异常表达有关。Objective To investigate genetic etiology of fetal urinary abnormalities with array-based comparative genomic hycridization （array-CGH）. Methods Thirty-two fetuses with variable urinary abnormalities but normal karyotyping by conventional cytogenetic technique were selected. DNA from the fetuses and their parents samples were prepared and hybridization with Affymetrix cytogenetic 2.7M arrays by follwing the manufacture＇ s standard protocol. The data were analyzed by special CHAS software packages. Results By using array-CGH detection, genomic imbalanced copy number variations （CNVs） were identified in night fetuses（28%）, four out of night CNVs were inherited from parental samples; two were indicated to be benign variants（6 % ） in the database; and the other three CNVs （9 % ）were all de novo adjacent microdeletions and mieroduplication mapping on to common chromosome lq21. 1 region, within which was genitourinaty system function associated gene PDZK1. Conclusion The incidence of genomic unbalanced variations in fetuses with congenital urinary malformations is approximately 28%, including about 9% pathogenic variations. Copy number variations （CNVs） of chromosome lq21. 1 region are associated with congenital urinary malformations which may be due to haploinsufficiency or overexpression of PDZK1 gene.

关 键 词：产前诊断 泌尿系统畸形 1q21.1微缺失/微重复 PDZK1基因 

分 类 号：R714.5[医药卫生—妇产科学]