一例9p正向重复伴末端缺失综合征胎儿的遗传学分析  

Genetic study of a fetus with 9p direct duplication deletion syndrome

作　　者：史珊珊[1] 林少宾[3] 楼湘莹[2] 李玮璟[1] 

机构地区：[1]暨南大学附属第一医院胎儿医学科,广州510630 [2]暨南大学附属第一医院妇产科,广州510630 [3]中山大学附属第一医院胎儿医学中心,广州510080

出　　处：《中华医学遗传学杂志》2017年第3期419-422,共4页Chinese Journal of Medical Genetics

摘　　要：目的应用下一代测序（next generation sequencing,NGS）技术鉴定1例G显带核型分析无法完全辨别的胎儿9号衍生染色体，探讨其重排的机制以及基因型与表型的对应关系。方法采集1例超声提示胎儿异常的孕妇的羊水样本进行G显带染色体核型分析，同时分析其亲代外周血的染色体核型。通过脐血穿刺术获取胎儿脐血样本进行NGS检测。结果胎儿羊水细胞的染色体核型为46，XX，der（9）（？：：p21→qter），其父母染色体核型均未见异常。胎儿脐血的NGS检测发现9p21．3p24．2（4454279—25126275）重复和9p24．2p24．3（10001—4442364）缺失，长度分别为20．67Mb和4．43Mb。前者覆盖9p重复综合征的致病区域，后者与9p缺失综合征致病区域部分重叠，并覆盖了46，XY sex reversal 4的致病区域。将测序数据通过数据库进行比对分析，提示9p21．3p24．2重复为正向重复。回顾分析9p21．3p24．2片段重复的形态特征，也证实9p21．3p24．2重复为正向重复。因此，胎儿的核型最终被确定为46，XX，der（9）dirdup（9）（p21．3p24．2），del（9）（p24．2p24．3）。结论将G显带染色体核型分析与NGS相结合，可以有效地鉴定dir dup del（9p）。分析dir dup del（9p）的形成机制及其基因型与表型的关联，可以为临床遗传咨询和再发风险评估提供参考。Objective To use next generation sequencing （NGS） to identify unknown abnormality of chromosome 9 in a fetus and explore its mechanism. Methods 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. Results Analysis of amniocytes has revealed a 46, XX,der（9）（？ ：： p21→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）. Conclusion 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.

关 键 词：9p正向重复伴末端缺失 胎儿 下一代测序 

分 类 号：R440[医药卫生—诊断学] R714.5[医药卫生—临床医学]