Department of Obstetrics, First Hospital of Changsha, Changsha 410005.
Department of Obstetrics, Xiangya Hospital, Central South University, Changsha 410008.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2021 Dec 28;46(12):1370-1374. doi: 10.11817/j.issn.1672-7347.2021.210412.
The 17q12 microdeletion syndrome is a type of syndrome caused by a deletion of 1.4 to 1.8 Mb in the 17q12 region of the chromosome. The main clinical features of the syndrome are structural or functional abnormalities in the kidney and urethra, type 5 diabetes, and neurodevelopmental or neuropsychiatric disorders. The diverse range of phenotypes associated with 17q12 microdeletion limited clinical recognition and diagnosis. In addition, the phenotypic description of this microdeletion is mainly about postpartum. Due to the rarity of the 17q12 microdeletion itself, studies on the prenatal phenotype of the 17q12 microdeletion are limited. This study aims to analyze the prenatal ultrasound features of 17q12 microdeletion, and to investigate the possibility of genotype-phenotype relationship for providing evidence for genetic counseling in such pregnancies.
A total of 3 320 pregnant women and their fetuses were collected for the detection of chromosome copy number variation sequencing (CNV-Seq) due to different ultrasound anomalies in Xiangya Hospital of Central South University. The clinical data of pregnant women and their fetuses who were found to harbor 17q12 microdeletion were reviewed, including maternal age, fetus ultrasound findings, gestational week of the invasive procedure, CNV-Seq results, and the pregnancy outcome. CNV-Seq was tested in the parents to verify whether the abnormality was de novo or inherited. The prenatal ultrasound features and CNV-Seq test results of these 12 fetuses were analyzed and their pregnancy outcomes were followed up.
Approximately 0.36% (12/3 320) of fetuses were detected to have 17q12 microdeletion, all characterized as renal abnormalities, accounting for 4.2% (12/288) of all prenatal ultrasound with renal abnormalities, accounting for 48% (12/25) of prenatal ultrasound with renal abnormalities and pathogenic chromosomal abnormalities. The sizes of 17q12 deletion ranged from 1.4 to 1.7 Mb, and all of them included the HNF1B gene. Nine cases were de novo, 2 inherited from the mother, and 1 inherited from father. Among 12 fetuses with 17q12 deletion, 11 cases of prenatal ultrasound suggested bilateral hyperechogenic kidneys and 1 case only showed renal cyst, in which 3 fetuses with enlarged kidneys, 1 with clubfeet, and 1 with subependymal cyst. Pregnancy outcomes were available for 11 of the 12 fetuses. Of them, the parents of 9 fetuses with de novo deletion chose to terminate the pregnancy, and 2 live birth babies inherited from their mother with normal renal function had persistent renal echogenicity enhancement after birth.
Bilateral hyperechogenic kidneys show strikingly correlation with 17q12 microdeletion, suggesting the necessity of chromosome copy numbers detection for fetuses with hyperechogenic kidneys.
17q12 微缺失综合征是一种由染色体 17q12 区域 1.4 至 1.8 Mb 缺失引起的综合征。该综合征的主要临床特征是肾脏和尿道的结构或功能异常、5 型糖尿病以及神经发育或神经精神障碍。17q12 微缺失与多种表型相关，这限制了临床识别和诊断。此外，这种微缺失的表型描述主要是产后。由于 17q12 微缺失本身的罕见性，对 17q12 微缺失的产前表型的研究有限。本研究旨在分析 17q12 微缺失的产前超声特征，并探讨基因型-表型关系的可能性，为该类妊娠的遗传咨询提供证据。
收集了 3320 名因不同超声异常在中南大学湘雅医院进行染色体拷贝数变异测序（CNV-Seq）检测的孕妇及其胎儿。回顾了发现携带 17q12 微缺失的孕妇及其胎儿的临床资料，包括孕妇年龄、胎儿超声发现、侵袭性手术的孕周、CNV-Seq 结果和妊娠结局。对父母进行 CNV-Seq 检测以验证异常是新发还是遗传。分析了这 12 例胎儿的产前超声特征和 CNV-Seq 检测结果，并对其妊娠结局进行了随访。
约 0.36%（12/3320）的胎儿被检测出携带 17q12 微缺失，均表现为肾脏异常，占所有产前超声发现肾脏异常的 4.2%（12/288），占所有产前超声发现肾脏异常和致病性染色体异常的 48%（12/25）。17q12 缺失的大小为 1.4 至 1.7 Mb，均包含 HNF1B 基因。9 例为新发，2 例遗传自母亲，1 例遗传自父亲。在 12 例携带 17q12 缺失的胎儿中，11 例产前超声提示双侧肾脏回声增强，1 例仅表现为肾囊肿，其中 3 例胎儿肾脏增大，1 例足内翻，1 例室管膜下囊肿。12 例胎儿中有 11 例的妊娠结局可用。其中，9 例新发缺失胎儿的父母选择终止妊娠，2 例从母亲遗传的活产婴儿出生后肾功能正常，但仍持续存在肾脏回声增强。
双侧肾脏回声增强与 17q12 微缺失具有显著相关性，提示对于回声增强的胎儿有必要进行染色体拷贝数检测。
