CAJ | 학술논문

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Affymetrix cytogenetic 2.7M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1q21.1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.
목적 응용미진렬비교기인조잡교기술탐토태인선천성비뇨계통기형적유전학병인.방법 선취32례경산전초성검사제시발생불동정도비뇨계통기형병차상규G현대핵형분석방법미발현이상적태인병례급기부모적DNA,안조표준적Affymetrix cytogenetic 2.7M심편적조작수책진행잡교、세조급전기인조소묘,응용배투적CHAS연건분석결과.결과 미진렬비교기인조잡교기술검측발현9례태인기인조발생료불평형적고패수변이(copy number variations,CNVs),검출솔위28％.기중4례CNVs유전자친대(12.5％)；2례CNVs재상관수거고중제시재정상인기인조중존재(6％)；3례시신발적치병성CNVs(9％),병차저3례태인양본균발생료염색체1q21.1미결실화미중복,이상편단내포함여비뇨생식계통공능밀절상관적PDZK1기인.결론 선천성비뇨계통기형태인기인조발생불평형기변적궤솔약위28％,기중치병성적기인조불평형이상약점9％.염색체1q21.1구대DNA고패수개변시도치선천성비뇨계통기형적병인지일,기치병궤제가능여PDZK1기인적이상표체유관.
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 microduplication mapping on to common chromosome 1q21.1 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 1q21.1 region are associated with congenital urinary malformations which may be due to haploinsufficiency or overexpression of PDZK1 gene.