摘要
目的通过对5例环状染色体综合征患者进行细胞遗传学分析,探讨高分辨率G显带核型分析和微阵列比较基因组杂交两种方法对环状染色体的诊断优势,并探讨5例环状染色体综合染色体缺失片段和定位于其中的基因与临床表型的关系。方法 2017年就诊于深圳市妇幼保健院的5例环状染色体综合征病例纳入研究。用染色体G带高分辨显带和微阵列比较基因组杂交技术对5例环状染色体进行识别与定位。结果病例1羊水染色体核型结果:45,XN,-18[13]/46,XN,r(18)(p11.2q22.3)[47],羊水微阵列比较基因组杂交结果:arr[GRCH37]18q22.3q23(70,063,358-78,013,728)x1;18p11.32p11.23(136,227-8,002,810)x1;18p11.23p11.22(8,013,797-8,877,061)x3。病例2脐血染色体核型结果:46,XN,rec(21)r(21q)dup(21q)(q11.2-q22.2)?,脐血微阵列比较基因组杂交结果:arr[GRCH37]21q11.2q22.3(15,016,486-47,044,951)x2~4;32MB.21q22.3(47,052,734-48,093,361)x1。病例3脐血染色体核型结果:45,XY,-21[14]/46,XN,r(21)[86],脐血微阵列比较基因组杂交结果:arr[GRCh37]21q11.2q22.3(15016486_47632178)x3[0.47];21q22.3(47632178_48093361)x1。病例4羊水染色体核型结果:46,XX,r(4)(p16q35),羊水微阵列比较基因组杂交结果:arr[GRCH37]4p16.3p16.1(68,345-8,721,580)x1;4q35.2(190,602,426-190,957,460)x1。病例5羊水染色体核型结果:mos45,X[46]/46,x,r(x)(p22.3q21.1)[34],羊水微阵列比较基因组杂交结果:Xq21.1q28(82119329_155233098)x1;Xp22.33p22.32(168551_5677733)x1;Xp22.32q21.1(5677733-82119329)x1[0.4]。结论 (1)环状染色体综合征患儿的临床特征与染色体区带缺失重复部位和大小相关。(2)G显带核型分析和微阵列比较基因组杂交诊断环状染色体各有优势:第一传统的G显带核型分析首先可判断是否存在嵌合的染色体核型;第二即使微阵列比较基因组结果提示染色体仅有长臂或短臂的缺失,也不能排除环状染色体的可能,亦需要传统的G显带染色体核型共同分析;第三微阵列比较基因组杂交能够精确基因组微小缺失和重复,利于基因组拷贝数变异与临床表型分析。因此联合G显带核型分析和微阵列比较基因组杂交对于环状染色体的诊断和遗传咨询具有指导意义。
Objective:To assess 5 prenatal cases with ring chromosome using both G-banding karyotype analysis and microarray comparative genomic hybridization;To explore diagnostic advantages of the two methods;To search the correlation between the genotype and the clinical phenotype on the 5 ring chromosome cases. Methods:Five fetuses were enrolled in this study. Identification and location of ring chromosome were performed with G-banding karyotype and microarray comparative genomic hybridization. Results:The karyotype of case 1 was 45,XN,-18[13]/46,XN,r(18)(p11.2 q22.3)[47],the aCGH revealed arr[GRCH37] 18 q22.3 q23(70,063,358-78,013,728)×1;18 p11.32 p11.23(136,227-8,002,810)×1;The karyotype of case 2 was46,XN,rec(21)r(21 q)dup(21 q)(q11.2-q22.2)?,the aCGH revealed arr[GRCH37]21 q11.2 q22.3(15,016,486-47,044,951)×2~4;32 MB.21 q22.3(47,052,734-48,093,361)x1;The karyotype of case 3 was45,XY,-21[14]/46,XN,r(21)[86],the aCGH revealed arr[GRCh37] 21 q11.2 q22.3(15016486 _476 32178)×3[0.47];21 q22.3(47632178_48093361)×1;The karyotype of case 4 was46,XX,r(4)(p16 q35),the aCGH revealed arr[GRCH37]4 p16.3 p16.1(68,345-8,721,580)×1;4 q35.2(190,602,426-190,957,460)×1;The karyotype of case 5 was mos45,X[46]/46,X,r(x)(p22.3 q21.1)[34],the aCGH revealed Xq21.1 q28(82119329_155233098)×1;Xp22.33 p22.32(168551_5677733)×1;Xp22.32 q21.1(5677733-82119329)x1[0.4].Conclusions:Phenotype associated with ring chromosomes were extreme variable by multiple factors,including the highly variable extent and location,and the presence of duplications. And our data confirm the importance of G-banding karyotype and microarray comparative genomic hybridization to determine the ring chromosome morphology and content.
引文
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