目的 探讨常规G显带染色体核型分析及染色体微阵列分析（chromosomal microarray analysis，CMA）技术在先天性泌尿系统畸形胎儿产前诊断中的应用价值及发病相关性，探讨泌尿系统畸形可能的致病机制。方法 回顾性研究134例产前超声检查发现胎儿泌尿系统畸形并行常规G显带染色体核型分析的病例，其中30例按照Affymetrix CytoScan HD 芯片平台的操作手册对胎儿及部分父母的DNA进行消化、连接、PCR、片段化、标记、杂交、洗染并全基因组扫描，采用配套的CHAS软件进行结果分析。结果 ①134例泌尿系统畸形病例，128例胎儿染色体正常；2例异常，分别为46,XY,del（21）（qter-p11：），46,XY,der（22）t（Y,22）（q11；q13.3），4例染色体多态性，染色体异常率为1.50%（2/134）。②30例CMA结果均成功获得分析，19例结果正常，检出11例CNVs，CNVs检出率为36.7%（11/30）；30例行CMA检测病例仅一例常规染色体核型分析异常（CMA亦检出病理性CNVs），余29例均正常，泌尿系统畸形但染色体核型正常胎儿CNVs检出率为34.5%（10/29）。③11例CNVs，20%（6/30）考虑为良性CNVs，16.7%（5/30）为病理性CNVs。6例良性CNVs胎儿，其中5例行父母亲外周血CMA检测，发现均为来源父系或母系的遗传。5例病理性CNVs胎儿，有3例行父母外周血CMA检测，发现均为新发CNVs。29例泌尿系统畸形但染色体核型正常胎儿的病理性CNVs检出率为13.8%（4/29）。④根据产前超声表现将30例泌尿系统畸形病例分为孤立性泌尿系统畸形（24例）和泌尿系统畸形合并其他畸形（6例），孤立性泌尿系统畸形胎儿的CNVs检出率为37.5%（9/24），其中病理性CNVs为20.8%（5/24），合并其他畸形胎儿的CNVs检出率为33.3%（2/6），无病理性CNVs。两组病理性CNVs检出率差异无统计学意义。（5）本研究检出1例新发的17q12缺失综合征病例，与肾囊肿和糖尿病综合征（renal cysts and diabetes syndrome，RCAD）重叠，内含与肾脏发育密切相关的HNF1β基因。结论 泌尿系统畸形胎儿常规染色体核型异常发生率为1.50%。通过CMA技术发现泌尿系统畸形但常规染色体核型正常胎儿CNVs检出率为34.5%，其中16.7%为病理性CNVs，CMA可明显提高遗传性疾病的诊断率。本研究发现孤立性泌尿系统畸形和多发系统畸形胎儿的病理性CNVs检出率差异无统计学意义。17q12缺失综合征可能是导致先天性泌尿系统畸形的原因之一，其发病与HNF1β基因单剂量不足相关。
Objective To study the clinical value of G banding karyotype analysis and CMA in prenatal diagnosis of congenital abnormalities of the urinary system. Method A retrospective study of 134 cases of fetal urinary tract abnormalities by prenatal ultrasonography and performed by G banding karyotype analysis. Results ①134 cases of urinary system abnormalities, 128 cases of normal fetal chromosome; 2 cases were abnormal, were 46, XY, del (21) (qter-p11), 46, XY, der (22) t (Y, 22) (Q11; q13.3), 4 cases of chromosome polymorphism and abnormal rate of chromosome is 1.50% (2/134). ②Results of 30 cases of CMA were successfully analyzed. In 19 cases, the results were normal. 11 cases of CNVs were detected, and the detection rate of CNVs was 36.7% (11/30). ③Of 11 patients with CNVs, 20% (6/30) considered benign CNVs, and 16.7% (5/30) were pathological CNVs.④According to the prenatal ultrasonic results, 30 cases of urinary abnormalities were divided into solitary urinary abnormalities (24 cases) and urinary abnormalities associated with other abnormalities (6 cases).⑤This study detected 1 cases of newly diagnosed 17q12 deletion syndrome, which overlapped with RCAD, and contained HNF1β gene closely related to renal development. Conclusions The incidence of chromosomal abnormalities in the abnormal fetus of urinary system was 1.50%. The urinary system abnormalities were detected by CMA, but the normal karyotype of fetal CNVs was 34.5%, 16.7% of which were pathological CNVs, and CMA could significantly improve the diagnostic rate of hereditary diseases.
