多囊性肾发育不良胎儿的染色体微阵列分析

Application of chromosome microarray analysis for fetuses with multicystic dysplastic kidney

目的应用染色体微阵列分析技术（ chromosome microarray analysis,CMA）在全基因组水平分析多囊性肾发育不良胎儿（multicystic dysplastic kidney, MCDK）的遗传学病因。方法选取产前超声提示MCDK伴或不伴其他肾外异常的胎儿样本72例进行常规G显带染色体核型分析，并对其中部分病例进行基因组DNA检测，应用ChAS软件和相关生物信息学数据库对结果进行分析。结果G显带染色体核型分析结果显示3例（4．2％）胎儿核型结果异常。在69例染色体核型分析结果为正常的胎儿中，对30例（43．5％）胎儿进行了CMA检测。CMA在5例（16．7％）胎儿中检出了致病性拷贝数变异（copy number variations，CNVs），分别为17q12微缺失综合征、Williams-Beuren综合征、4q35．2微缺失、22q13．33微重复和1p33微重复。对比DECIPHER及OMIM数据库分析，其中22q11区的PEX26基因、7q11．23区的FKBP6基因、22q13．33区的ALG12和TUBGCP6基因以及1p33区的CYP4A11基因为新发现的MCDK候选基因。结论CMA可显著提高MCDK胎儿遗传学病因的检出率，不仅能够确定G显带核型分析所发现的异常片段来源、长度以及性质，还能够检测G显带核型分析所无法识别的微缺失／微重复，同时还能发现新的候选基因，为MCDK胎儿的产前诊断、咨询以及预后评估提供依据。

Objective To explore the genetic etiology of fetuses with multicystic dysplastic kidney （MCDK） by chromosome mieroarray analysis （CMA）. Methods Seventy-two fetuses with MCDK were analyzed with conventional cytogenetic technique, among which 30 fetuses with a normal karyotype were subjected to CMA analysis with Affymetrix CytoScan HD arrays by following the manufacturer＇s protocol. The data was analyzed with ChAS software. Results Conventional cytogenetic technique has revealed three fetuses （4.2%） with identifiable chromosomal aberrations. CMA analysis has detected pathogenic CNVs in 5 fetuses （16. 7%）, which included two well-known microdeletion or microduplieation syndromes, i. e. , 17q12 microdeletion syndrome and Williams Beuren syndrome （WBS） and three submicroscopic imbalances at 4q35. 2, 22q13. 33, and 1p33. PEX26, FKBP6, TUBGCP6, ALG12, and CYP4A11 are likely the causative genes. Conclusion CMA can identify the submicroscopic imbalances unidentifiable by conventional eytogenetic technique, and therefore has a significant role in prenatal diagnosis and genetic counseling. The detection rate of pathogenic CNVs in fetuses with MCDK was 16. 7% by CMA. 17q12 microdeletion syndrome and WBS are associated with MCDK. Mutations of PEX26, FKBP6, TUBGCP6, ALG12, and CYP4A11 genes may be the causes for MCDK.