目的 通过对孕妇羊水进行染色体核型、荧光原位杂交(fluorescence in situ hybridization,FISH)分析,探讨两者联合检测在诊断罗伯逊易位型21-三体中的应用价值.方法 为2010年1月至2011年12月进行产前诊断的孕妇抽取羊水,经体外细胞培养后进行G显带染色体核型分析.对发现的5例罗伯逊易位采用FISH检测间期细胞13、18、21及X/Y的染色体数目,并分析孕妇及其丈夫外周血染色体核型.结果 两个胎儿父母外周血染色体核型正常,其中一个胎儿羊水染色体核型为46,XY,rob(21；21)(q10;q10),FISH检测提示其为21-二体,另一个胎儿核型为46,XY,rob(14;21)(q10；q10),FISH检测证实其为21-三体.另外3个胎儿母亲外周血染色体核型分别为45,XX,rob(14;21)(q10;q10)、45,XX,rob(15;21)(q10;q10)、45,XX,rob(21; 22) (q10; q10),其羊水染色体核型分别为46,XX,rob(14;21)(q10;q10)、46,XY,rob(15;21) (q10;q10)、46,XX,rob(21;22)(q10;q10).FISH检测证实其均为21-三体.结论 染色体核型分析结合FISH检测有助于明确罗伯逊易位型21-三体的诊断,但FISH检测同源罗伯逊易位型21-三体征有一定局限性.

Objective To assess the value of fluorescence in situ hybridization (FISH) combined with chromosomal analysis for the detection of Robertsonian translocation type trisomy 21 in amniotic fluid cells.Methods Amniotic fluid samples from pregnant women requesting prenatal diagnosis were cultivated.Metaphase cells were prepared for G-banding karyotype analysis.For the 5 Robertsonian translocation type trisomy 21,interphase nuclei from amniotic fluid and parental peripheral blood cells were prepared for FISH analysis.Results In 2 cases,analysis of parental peripheral blood cells showed normal karyotypes.FISH analysis of amniotic fluid cells indicated that one sample had two copies of chromosome 21,which has a 46,XY,rob(21 ; 21) (q10 ; q10) karyotype,whilst another had trisomy 21 by FISH,which has a 46,XY,rob (14;21) (q10;q10) karyotype.For the remaining three samples,analysis of parental peripheral blood cells indicated that their karyotypes were 45,XX,rob(14;21)(q10;q10),45,XX,rob(15;21)(q1

目的 明确1例多发畸形患儿染色体拷贝数变异的性质及来源,分析其染色体变异与表型的相关性.方法 首先应用常规G显带分析该例患儿及父母外周血染色体核型,然后应用比较基因组杂交芯片(array comparative genomic hybridization,array CGH)技术对该例常规核型分析的结果进行精确定位.结果 该患几常规核型分析为46,XY.array CGH结果为del(5) (p15.2p15.33)区段存在14.21 Mb缺失；dup(5) (q35.3)区段存在3.67 Mb重复.临床表现为智力低下、特殊面容、同时伴有小头畸形、先天性心脏病及脚趾畸形等.患儿父母亲染色体核型正常.结论 5号染色体拷贝数变异可导致患儿出现多发畸形；与传统的细胞遗传学分析方法相比,array CGH在染色体异常分析中具有更高的分辨率和准确性.

Objective To determine the origin of chromosomal aberration for a child featuring multiple malformation,and to correlate the genotype with phenotype.Methods Routine G-banding was performed to analyze the karyotype of the patient and her parents,and array comparative genomic hybridization (array CGH) was used for fine mapping of the aberrant region.Results The karyotype of the child was ascertained as 46,XY.Array CGH has mapped a 14.21 Mb deletion to 5p15.2p15.33,and a very small 3.67 Mb duplication to 5q35.3.The patient has presented features such as mental retardation,heart defect,low-set ears,hypertelorism and down-slanting palpebral fissures.Conclusion Chromosome 5 copy number variation can cause multiple malformation.In contrast to routine karyotype analysis,array CGH can map aberrant region with much higher resolution and accuracy.

目的 报道1例初发伴有rob(13;21) t(15;17)(q22;q21)的急性早幼粒细胞白血病(APL)并探讨其临床和实验室特点.方法 在常规核型分析和骨髓细胞形态学的基础上,应用双色双融合荧光原位杂交(DCDF-FISH)和RT-PCR技术进一步检测该患者的细胞遗传学异常和分子生物学异常.并结合文献分析此类伴少见变异易位APL患者的临床特点.结果 患者的临床表现和骨髓细胞形态学检查均符合APL.初诊时免疫表型分析髓系标志呈阳性,R显带染色体分析显示患者核型为45,XX,rob(13;21)t(15; 17) (q22;q21) [6]/45,XX,rob(13;21)[14],FISH结果显示68.9％的细胞为典型的t(15;17)模式,RT-PCR结果显示PML-RARα融合基因水平为25.8％.经诱导化疗、巩固治疗后,达到完全缓解,核型为45,XX,rob(13;21) [20],FISH检测PML-RARα融合基因阳性细胞率为2.5％,PML-RARα融合基因水平为0.003％.结论 伴特征性的rob(13;21)t(15;17)(q22;q21)的APL十分罕见,患者临床表现和实验室检查基本符合APL的临床特点;该染色体异常对APL患者的预后判断价值仍需进一步的观察.

Objective To report an acute promyelocytic leukaemia (APL) case with translocation of rob (13 ;21) t(15;17) (q22;q21) and review its clinical and laboratory characteristics.Methods Based on routine karyotype analysis and bone marrow morphology,we further used double color double fluorescent in situ hybridization (DCDF-FISH) and reverse transcriptase PCR (RT-PCR) to examine the patient'' s abnormities on cytogenetic and molecular biology,and reveal the clinical characteristics of this rare translocation also from the related literatures.Results The clinical manifestation and bone marrow morphology examination of this patient were in accordance with pathologic feature of APL.On first visit,immunophenotyping analysis showed positive myeloid markers.Through R-banding,the patient'' s karyotype was confirmed as 45,XX,rob (13;21) t (15;17) (q22;q21) [6] / 45,XX,rob (13;21) [14].FISH results showed that 68.9％ cells were typical t (15;17) pattern.The positive rates of fusion gene of

目的 评估高分辨微阵列比较基因组杂交技术(Array CGH)在临床复杂染色体异常遗传诊断中应用的可行性.方法 选取2010年12月至201 1年12月厦门市妇幼保健院遗传咨询门诊患者2例、产前诊断门诊患者2例.2例遗传咨询患者按无菌要求、EDTA抗凝,采集2～4 ml外周血；2例产前诊断患者,经遗传咨询、术前检查后,于手术室B超引导下抽取约2～3ml脐血.对4份标本分别进行染色体核型分析,同时提取4份标本的全基因组DNA,应用Array CGH进行亚显微水平分析.Array CGH结果最后通过荧光原位杂交技术(FISH)进行验证.结果 Array CGH检测发现4例患者在多条染色体上均出现不同程度的复制和缺失,这些复制和缺失大多数没有被核型分析检测到.1号病例为4p16.3-4p15.31复制、4p16.3端粒区缺失；2号病例为Xp11.22-Xq11.1复制；3号病例为2q37.3缺失、4p16.3-4p15.32复制；4号病例为2q14.3-2q21.1缺失、2q21.2-2q32.1复制.FISH检测与Array CGH结果相吻合.结论 Array CGH可以准确检测亚显微的微小片段缺失、复制等拷贝数变化,且能确定断裂位点,可为临床遗传诊断提供依据.

Objective To evaluate application feasibility of Array CGH in genetic diagnosis of clinical complex chromosomal abnormalities.Methods Two patients of genetic counseling and two patients of prenatal diagnosis were selected from Xiamen Maternity & Child Health Care Hospital during the period of December 2010 to December 2011.Under aseptic conditions 2-4 ml peripheral blood was collected in EDTA and 2-3 ml Cord Blood was collected through cordocentesis after genetic counseling and preoperative examination.G-banded chromosome analysis and genome DNA extraction were carried out on the four cases.The whole genome of four cases were scanned and analyzed by Array CGH.The results of Array CGH were confirmed by FISH.Results Array CGH detected different kinds of duplications and deletions in several chromosomes.Most of these duplications and deletions were not detected by karyotype analysis.The results of Array CGH showed duplication of 4p16.3-4p15.31,deletion of 4p16.3 in the first cas