Shi Shanshan, Lin Shaobin, Lou Xiangying, Li Weijing
Fetal Medicine Center, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017 Jun 10;34(3):419-422. doi: 10.3760/cma.j.issn.1003-9406.2017.03.024.
To use next generation sequencing (NGS) to identify unknown abnormality of chromosome 9 in a fetus and explore its mechanism.
A pregnant woman with abnormal fetal ultrasound finding underwent amniocentesis for G-banded chromosomal analysis. Karyotyping was also performed on peripheral blood samples derived from its parents. Fetal blood sample was obtained for NGS testing to identify abnormality unrecognized by karyotyping.
Analysis of amniocytes has revealed a 46,XX,der(9)(?::p21 to qter) karyotype, while both parents had a normal karyotype. NGS analysis of the fetus revealed a 20.67 Mb duplication (4 454 279-25 126 275) at 9p21.3p24.2, which overlapped with that of the 9p duplication syndrome, and a 4.43 Mb deletion at 9p24.2p24.3 (10 001-4 442 364), which partially overlapped with that of 9p deletion syndrome and 46,XY sex reversal 4 region. Comparison of the sequencing data with reference genome database indicated direct duplication of 9p21.3p24.2, which was also supported by review of the morphology of chromosome 9p. Therefore, the karyotype of the fetus was verified to be 46,XX,der(9) dir dup(9)(p21.3p24.2), del(9)(p24.2p24.3).
Combined G-banded karyotyping and NGS can identify dir dup del(9p) with accuracy. Delineation of the mechanism of dir dup del(9p) and its genotype-phenotype correlation may facilitate genetic counseling and estimation of recurrence risk.
运用新一代测序技术（NGS）鉴定胎儿9号染色体的未知异常情况并探究其机制。
一名胎儿超声检查异常的孕妇接受了羊水穿刺以进行G显带染色体分析。同时对其父母的外周血样本进行了核型分析。获取胎儿血样进行NGS检测以鉴定核型分析未识别出的异常情况。
羊水细胞分析显示胎儿核型为46,XX,der(9)(?::p21至qter)，而其父母核型均正常。胎儿的NGS分析显示在9p21.3p24.2处有一个20.67 Mb的重复（4 454 279 - 25 126 275），与9p重复综合征的区域重叠，以及在9p24.2p24.3处有一个4.43 Mb的缺失（10 001 - 4 442 364），部分与9p缺失综合征和46,XY性反转4区域重叠。将测序数据与参考基因组数据库进行比较表明9p21.3p24.2存在直接重复，这也得到了9号染色体短臂形态学检查的支持。因此，胎儿的核型被确认为46,XX,der(9) dir dup(9)(p21.3p24.2), del(9)(p24.2p24.3)。
联合G显带核型分析和NGS能够准确鉴定9p的直接重复缺失。阐明9p直接重复缺失的机制及其基因型 - 表型相关性可能有助于遗传咨询和复发风险评估。
