应用细胞和分子遗传学技术检测一例嵌合型21q部分三体

Cytogenetic and molecular genetic analysis of a fetus with mosaic partial trisomy 21q

目的:对一例无创产前检测(NIPT)中检出的21三体高风险病例进行产前诊断,明确其遗传学异常,为遗传咨询提供参考。方法:应用染色体G显带技术进行核型分析、多重荧光定量聚合酶链反应(QF⁃PCR)和单核苷酸多态性微阵列芯片(SNP⁃array)技术检测额外小标记染色体(sSMC)的来源和成分。结果:胎儿染色体核型为47,XN,+mar1[86]/48,XN,+mar1,+mar2[14],为新发变异。QF⁃PCR提示胎儿21号染色体的5个STR位点存在拷贝数异常,即21q21.1q22.11区域的D21S11、D21S1437和D21S2039存在嵌合三体,21q22.2q22.3区域的D21S1412和D21S1411存在三体型。SNP⁃array的检测结果为arr[GRCh37]21q11.2q22.2(15016487_40158518)×2⁃3(嵌合比例约35%),21q22.2q22.3(40174787_48093361)×3。结论:在产前诊断中应该联合应用多种检测手段,取长补短,才能更准确地进行诊断。

Objective:To present the prenatal diagnosis of a high⁃risk case of trisomy 21 detected in noninvasive prenatal testing(NIPT),clarify its genetic abnormalities,and provide reference for genetic counseling.Methods:Chromosome G⁃banding techniques were used for karyotype analysis.Multiplex fluorescent quantitative polymerase chain reaction(QF⁃PCR)and single nucleotide polymorphism microarray(SNP⁃array)were used to trace the source of small supernumerary marker chromosomes(sSMC)and components.Results:The karyotype of the fetal chromosome was 47,XN,+mar1[86]/48,XN,+mar1,+mar2[14],suggesting a de novo variation.QF⁃PCR showed abnormalities in copy number at five STR loci of the fetal chromosome 21,namely,chimeric trisomy at D21S11,D21S1437 and D21S2039 of 21q21.1q22.11,and trisomy at D21S1412 and D21S1411 of 21q22.2q22.3.The detection result of SNP array was arr[GRCh37]21q11.2q22.2(15016487_40158518)×2⁃3(about 35%of chimeric ratio)and 21q22.2q22.3(40174787_48093361)×3.Conclusion:In prenatal diagnosis,combined use of multiple detections should be useful in determining a more accurate diagnosis.