荧光原位杂交技术在产前诊断染色体嵌合体中的应用价值

目的:探讨荧光原位杂交技术(fluorescence in situ hybridization,FISH)在产前诊断染色体嵌合体中的应用。方法:22例行绒毛/羊水细胞体外培养染色体核型结果提示可能存在染色体嵌合现象的病例,进一步用染色体微阵列比较基因组杂交检测(chromosomal microarray analaysis,CMA)和FISH技术分析确定其异常核型及嵌合比例。结果:22例核型结果提示嵌合体的病例中,性染色体数目嵌合13例,常染色体三体嵌合6例,性染色体结构异常嵌合3例。近50%病例CMA结果未检测到嵌合现象,可能与CMA技术仅能检测基因拷贝数变化且无法检测低比例嵌合有关。因常染色体数目异常对胎儿生长发育影响较大,常染色体数目异常嵌合病例中,除1例病例外其余均选择终止妊娠。3例结构异常嵌合病例经核型分析结合CMA及FISH结果确定均为性染色体双着丝粒染色体复杂结构嵌合。结论:对于产前诊断提示可能存在染色体嵌合的病例,不应急于终止妊娠,需采用多种方法加以验证,应充分应用CMA技术和FISH技术结合G显带核型结果进行综合分析,并需要对胎儿形态进行细致的超声评估,从而更加准确地确定嵌合类型以及异常核型的嵌合比例,为临床医师指导遗传咨询提供更加可靠的依据。

Application of Fluorescence in situ Hybridization in Prenatal Diagnosis of Chromosomal Mosaicism

Objective: To explore the application of fluorescence in situ hybridization(FISH) in the prenatal diagnosis of chromosomal mosaicism. Methods:A total of 22 cases of potential chromosome mosaicism detected by the villus/aminotic cell G-band karyotype analysis were included in this study. The abnormities of chromosome karyotype and the ratio of chromosome mosaicism were further analyzed by chromosomal microarray analaysis(CMA) and FISH. Results:In those 22 cases, there were 13 cases of sex chromosome mosaicism, 6 cases of autosomal trisomy mosaicism and 3 cases of sex chromosome structure mosaicism. Almost 50% of chromosomal mosaicism were not found by CMA, which may be related to the fact that CMA can only detect the change of gene copy number and can not detect low ratio of chromosomal mosaicism. Because of great influence on the growth and development of fetus, cases of autosomal trisomy mosaicism were terminated except one case. Three cases of sex chromosome structure mosaicism were confirmed as the dicentric sex chromosome by the combined G-band, CMA and FISH. Conclusions:Multiple methods should be combined to verify the chromosomal mosaicism in those patients with the suspicious chromosomal mosaicism detected by the villus/aminotic cell G-band karyotype analysis in prenatal diagnosis. The combined application of CMA, FISH and G-band, as well as detailed ultrasound evaluation, is required. The accurate diagnosis of the chromosome mosaicism type and the ratio of abnormal mosaicism karyotype can provide a more reliable basis for genetic counseling.