PDF(Pubmed)
Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Bilateral hyperechogenic kidneys show strikingly correlation with 17q12 microdeletion, suggesting the necessity of chromosome copy numbers detection for fetuses with hyperechogenic kidneys.
目的: 17q12微缺失综合征是17号染色体长臂1区2带区域缺失1.4~1.8 Mb引起的一类综合征，主要临床特征为肾和尿道的结构或功能异常、5型糖尿病、神经发育异常及神经精神疾病。表型的多样性限制了临床的识别和诊断，目前对该微缺失表型的描述多是关于出生后的，并且因17q12微缺失本身的罕见性，对产前17q12微缺失表型的研究是有限的。本研究通过分析胎儿染色体17q12微缺失综合征的产前超声特征，探讨其产前超声表型与遗传学的相关性，为临床遗传咨询提供依据。方法: 回顾性分析因产前超声异常在中南大学湘雅医院行基因组拷贝数变异测序(copy number variation sequencing，CNV-Seq)检测的3 320例孕妇及胎儿资料，分析被诊断为染色体17q12微缺失综合征胎儿及其母亲的临床资料，包括孕妇年龄、胎儿超声检查结果、羊水穿刺的孕周、CNV-Seq检测结果和妊娠结局，并对胎儿的父母进行CNV-Seq检测以明确变异来源；分析胎儿的产前超声特征和CNV-Seq检测结果，并进行追踪随访。结果: 3 320例胎儿中有12例(0.36%)被检测出存在染色体17q12微缺失，均表现为肾异常，占所有产前超声提示肾异常胎儿的4.2%(12/288)，占产前超声提示肾异常且CNV-Seq结果为致病性染色体异常胎儿的48% (12/25)。12例17q12微缺失综合征胎儿缺失片段为1.4~1.7 Mb，其区域均涉及HNF1B基因，其中9例为新发突变，2例遗传自母亲，1例遗传自父亲。在12例17q12微缺失综合征的胎儿中，11例产前超声提示双肾回声增强，1例仅有肾囊肿；3例合并肾增大，1例合并足内翻，1例合并室管膜下囊肿。12例胎儿中获得11例胎儿的妊娠结局，其中9例新发突变的胎儿父母选择终止妊娠，2例遗传自母亲的胎儿出生后肾回声增强持续存在，肾功能正常。结论: 胎儿肾回声增强与染色体17q12微缺失有着高度的相关性，对肾回声增强的胎儿有必要进行染色体拷贝数检测。.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Bilateral hyperechogenic kidneys show strikingly correlation with 17q12 microdeletion, suggesting the necessity of chromosome copy numbers detection for fetuses with hyperechogenic kidneys.
目的: 17q12微缺失综合征是17号染色体长臂1区2带区域缺失1.4~1.8 Mb引起的一类综合征，主要临床特征为肾和尿道的结构或功能异常、5型糖尿病、神经发育异常及神经精神疾病。表型的多样性限制了临床的识别和诊断，目前对该微缺失表型的描述多是关于出生后的，并且因17q12微缺失本身的罕见性，对产前17q12微缺失表型的研究是有限的。本研究通过分析胎儿染色体17q12微缺失综合征的产前超声特征，探讨其产前超声表型与遗传学的相关性，为临床遗传咨询提供依据。方法: 回顾性分析因产前超声异常在中南大学湘雅医院行基因组拷贝数变异测序(copy number variation sequencing，CNV-Seq)检测的3 320例孕妇及胎儿资料，分析被诊断为染色体17q12微缺失综合征胎儿及其母亲的临床资料，包括孕妇年龄、胎儿超声检查结果、羊水穿刺的孕周、CNV-Seq检测结果和妊娠结局，并对胎儿的父母进行CNV-Seq检测以明确变异来源；分析胎儿的产前超声特征和CNV-Seq检测结果，并进行追踪随访。结果: 3 320例胎儿中有12例(0.36%)被检测出存在染色体17q12微缺失，均表现为肾异常，占所有产前超声提示肾异常胎儿的4.2%(12/288)，占产前超声提示肾异常且CNV-Seq结果为致病性染色体异常胎儿的48% (12/25)。12例17q12微缺失综合征胎儿缺失片段为1.4~1.7 Mb，其区域均涉及HNF1B基因，其中9例为新发突变，2例遗传自母亲，1例遗传自父亲。在12例17q12微缺失综合征的胎儿中，11例产前超声提示双肾回声增强，1例仅有肾囊肿；3例合并肾增大，1例合并足内翻，1例合并室管膜下囊肿。12例胎儿中获得11例胎儿的妊娠结局，其中9例新发突变的胎儿父母选择终止妊娠，2例遗传自母亲的胎儿出生后肾回声增强持续存在，肾功能正常。结论: 胎儿肾回声增强与染色体17q12微缺失有着高度的相关性，对肾回声增强的胎儿有必要进行染色体拷贝数检测。.
摘要：
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