Cai Meiying, Lin Na, Su Linjuan, Wu Xiaoqing, Xie Xiaorui, Li Ying, Chen Xuemei, Lin Yuan, Huang Hailong, Xu Liangpu
Department of the Prenatal Diagnosis Center, Fujian Provincial Maternity and Children's Hospital, affiliated hospital of Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.
Mol Cytogenet. 2020 Mar 24;13:11. doi: 10.1186/s13039-020-00481-7. eCollection 2020.
Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20-30% of all congenital malformations. Within the CAKUT phenotypic spectrum, renal hypodysplasia (RHD) is particularly severe. This study aimed to evaluate the applicability of single-nucleotide polymorphism (SNP) array test in prenatal diagnosis of RHD for improving prenatal genetic counseling and to search for evidence of a possible causative role of copy-number variations (CNVs) in RHD.
We performed a systematic survey of CNV burden in 120 fetuses with RHD: 103 cases were isolated RHD and 17 were non-isolated RHD. Single-nucleotide polymorphism (SNP) array test was performed using the Affymetrix CytoScan HD platform. All annotated CNVs were validated by fluorescence in situ hybridization. We identified abnormal CNVs in 15 (12.5%) cases of RHD; of these CNVs, 11 were pathogenic and 4 were variants of uncertain significance. The detection rate of abnormal CNVs in non-isolated RHD was higher (29.4%, 5/17) than that in isolated RHD (9.7%, 10/103) ( = 0.060). Parents are more inclined to terminate the pregnancy if the fetuses have pathogenic results of the SNP-array test.
The variable phenotypes that abnormal CNVs may cause indicate the genetic counseling is needed for RHD cases.
先天性肾和尿路畸形（CAKUT）占所有先天性畸形的20%-30%。在CAKUT表型谱中，肾发育不全（RHD）尤为严重。本研究旨在评估单核苷酸多态性（SNP）阵列检测在RHD产前诊断中的适用性，以改善产前遗传咨询，并寻找拷贝数变异（CNV）在RHD中可能致病作用的证据。
我们对120例RHD胎儿的CNV负担进行了系统调查：103例为孤立性RHD，17例为非孤立性RHD。使用Affymetrix CytoScan HD平台进行单核苷酸多态性（SNP）阵列检测。所有注释的CNV均通过荧光原位杂交进行验证。我们在15例（12.5%）RHD病例中鉴定出异常CNV；其中11例为致病性CNV，4例为意义未明的变异。非孤立性RHD中异常CNV的检出率（高达29.4%，5/17）高于孤立性RHD（9.7%，10/103）（P=0.060）。如果胎儿SNP阵列检测结果为致病性，父母更倾向于终止妊娠。
异常CNV可能导致的可变表型表明，RHD病例需要进行遗传咨询。
