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Abstract：
OBJECTIVE: This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism.
METHODS: For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD).
RESULTS: Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal.
CONCLUSIONS: In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7.
METHODS: For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD).
RESULTS: Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal.
CONCLUSIONS: In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7.
摘要：
目的：本研究旨在对通过非侵入性产前检测（NIPT）鉴定的7三体高危胎儿进行产前基因诊断，并评估不同基因检测技术在产前诊断三体镶嵌性方面的有效性。
方法：对于NIPT建议的7三体高风险孕妇的产前诊断，对羊水样本进行核型分析和染色体微阵列分析（CMA）。低深度全基因组拷贝数变异测序（CNV-seq）和荧光原位杂交（FISH）用于进一步阐明结果。此外,进行甲基化特异性多重连接依赖性探针扩增（MS-MLPA）以分析单亲二体性（UPD）的可能性。
结果：羊水核型分析显示46,XX结果。根据CMA结果检测到大约20%的镶嵌三体7。CNV-seq和FISH检测到约16%和4%的镶嵌性，分别。MS-MLPA未显示甲基化异常。除了在妊娠39周时看到的轻度宫内发育迟缓外，胎儿超声检查未显示任何可检测到的异常。在接受遗传咨询后，准妈妈决定继续怀孕,分娩后三个月内随访正常。
结论：在高风险NIPT诊断中，细胞遗传学和分子遗传学技术的结合证明了检测低水平镶嵌性的卓有成效。此外，当NIPT显示7三体的产前诊断为阳性时，排除7号染色体上的UPD仍然至关重要。
方法：对于NIPT建议的7三体高风险孕妇的产前诊断，对羊水样本进行核型分析和染色体微阵列分析（CMA）。低深度全基因组拷贝数变异测序（CNV-seq）和荧光原位杂交（FISH）用于进一步阐明结果。此外,进行甲基化特异性多重连接依赖性探针扩增（MS-MLPA）以分析单亲二体性（UPD）的可能性。
结果：羊水核型分析显示46,XX结果。根据CMA结果检测到大约20%的镶嵌三体7。CNV-seq和FISH检测到约16%和4%的镶嵌性，分别。MS-MLPA未显示甲基化异常。除了在妊娠39周时看到的轻度宫内发育迟缓外，胎儿超声检查未显示任何可检测到的异常。在接受遗传咨询后，准妈妈决定继续怀孕,分娩后三个月内随访正常。
结论：在高风险NIPT诊断中，细胞遗传学和分子遗传学技术的结合证明了检测低水平镶嵌性的卓有成效。此外，当NIPT显示7三体的产前诊断为阳性时，排除7号染色体上的UPD仍然至关重要。
