三例22号染色体异常胎儿的产前遗传学分析

目的应用超声以及多种遗传学检测技术对3例产前筛查提示染色体可能异常的胎儿进行分析,为遗传咨询提供依据。方法对3例孕妇进行胎儿超声检查、核型分析、单核苷酸多态性微阵列芯片(single nucleotide polymorphism-based microarray,SNP-Array)检测,并通过荧光原位杂交(fluorescence in situ hybridization,FISH)对结果进行验证。结果三例胎儿均发现22号染色体存在异常。例1在22q13.2q13.33区存在7.1 Mb的杂合缺失,涉及SHANK3、FBLN1等54个OMIM基因;例2为嵌合体核型,约12%的细胞22q13.31q13.33区存在6.6 Mb的杂合缺失,覆盖SHANK3、PPARA等48个OMIM基因,另有5%的细胞22q11.1q13.2区存在26.1 Mb的拷贝重复,覆盖285个OMIM基因;例3在22q11.1q11.21区存在1.7 Mb的二次重复,涉及CECR1、CECR2、ATP6V1E1等10个OMIM基因。三例胎儿父母的核型及SNP-Array检测结果均未见异常,提示胎儿为新发变异。结论22号染色体微缺失/微重复所致疾病的严重性不仅与其范围有关,还与染色体结构、基因剂量及环境等密切相关。在产前诊断中综合运用超声和多种遗传学检测技术可以显著提高表型变异较大的遗传学异常的检出率。

Prenatal genetic analysis of three fetuses with abnormalities of chromosome 22

Objective To carry out genetic testing for 3 fetuses with abnormal prenatal screening.Methods Fetal ultrasound,karyotype analysis,single nucleotide polymorphism(SNP)array and fluorescence in situ hybridization were performed.Results Abnormalities of chromosome 22 were found with all 3 fetuses.Fetus 1 harbored a 7.1 Mb deletion in 22q13.2q13.33 region,which involved 54 OMIM genes including SHANK3 and FBLN1.Fetus 2 had a mosaicism karyotype,with 12%of cells harboring a 6.6 Mb deletion in 22q13.31q13.33,covering 48 OMIM genes such as SHANK3 and PPARA,and 5%of cells harboring a 26.1 Mb duplication in 22q11.1q13.2 involving 285 OMIM genes.Fetus 3 carried a tandem duplication of 1.7 Mb in 22q11.1q11.21,which involved 10 OMIM genes including CECR1,CECR2 and ATP6V1E1.No abnormality was found in the three couples by chromosomal karyotyping and SNP array analysis.Conclusion The severity of diseases caused by chromosome 22 abnormalities not only depends on the range of the deletion or duplication,but is also closely related to chromosome structure,gene dose and genetic environment.Combined ultrasonography and various genetic testing techniques in prenatal diagnosis can greatly increase the detection rate of genetic diseases with substantial phenotypic variation.