BoBs技术在复杂先天性心脏病遗传学检测和病因研究中的应用

Application of BoBs Technology to the Genetic Detection and Etiologic Research of Complex Congenital Heart Disease

探讨细菌人工染色体标记微球阵列技术(BoBs)在揭示不明原因的复杂先天性心脏病遗传学病因中的应用价值,建立针对常见染色体微缺失/微重复综合征的快速临床检测技术策略.共采集了2014年4月-2018年11月间经超声心动图检查临床确诊的复杂先心病病例样本77例,使用产前BoBs技术分别检测患者在13、18、21、X和Y染色体的非整倍体变异,以及9个区域的微重复与微缺失变异,结果共检出染色体异常的阳性标本17例.其中染色体数目异常11例,包括13三体综合征1例,18三体综合征5例,21三体综合征3例,性染色体异常2例;以及染色体微缺失/微重复综合征6例,包括Miller-Dieker综合征合并Williams-Beuren综合征1例,Langer-Giedion综合征2例,DiGeorge微缺失综合征3例.产前BoBs技术作为一项高通量检测技术,用于特异性检测复杂先心病患者在13、18、21、X、Y染色体非整倍体变异和9个综合征区域的微重复与微缺失,具有获取结果快速、准确、简便的显著优势,为阐明复杂先心病的发病机制和临床干预提供了有效手段.

This article aims to explore the application of BAC-on-Beads(BoBs)technique in revealing the genetic etiology of complex congenital heart disease(CHD)with unknown cause,and establish a rapid clinical detection strategy for common chromosomal microdeletion/microduplication syndrome.In this study,a total of 77 patients with complex congenital heart disease were collected from April 2014 to November 2018,and clinically diagnosed by echocardiography.Aneuploid in 13,18,21,X and Y chromosomes,as well as chromosome microduplication and microdeletion variation in 9 regions were detected by prenatal BoBs.As a result,a total of 17 positive cases with chromosome abnormality were detected.There were 11 cases of chromosome numerical abnormality,including 1 case of trisomy 13 syndrome,5 cases of trisomy 18 syndrome,3 cases of trisomy 21 syndrome,2 cases of sex chromosome abnormality,and 6 cases of chromosomal microdeletion/microduplication syndrome,including 1 case of Miller-Dieker syndrome combined with Williams-Beuren syndrome,2 cases of Langer-Giedion syndrome,and 3 cases of DiGeorge microdeletion syndrome.As a high-throughput detection technology,prenatal BoBs is used to specifically detect aneuploid in chromosome 13,18,21,X,and Y,as well as microduplication and microdeletion of 9 syndrome regions in patients with complex CHD.It has significant advantages in obtaining results quickly,accurately,and simply.Moreover,prenatal BoBs also provides an effective means to elucidate the pathogenesis and to guide clinical intervention of complex CHD.