13号环状染色体合并长臂部分缺失嵌合核型1例的细胞遗传学分析

目的通过对1例13号环状染色体合并长臂部分缺失嵌合核型患者的遗传学分析,探讨13号环状染色体异常与临床表型的关系。方法应用细胞遗传学技术,对1例临床表现为发育不良的7岁女孩进行外周血染色体核型分析,并结合临床资料进行遗传学分析。结果患儿染色体异常为新发突变,外周血染色体核型为mos 46,XX,r(13)(p13q34)[218]/46,XX,del(13)(q14)[86]/45,XX,-13[41]/46,XX,dic r(13;13)(p13q34;p13q34)[20]/47,XX,-13,+dic r(13;13)(p13q34;p13q34)×2[6]。遗传学分析显示患儿13号染色体存在遗传物质的丢失与重复,不同核型嵌合比例存在差异。结论 13号环状染色体综合征临床表型多变,与染色体遗传物质丢失或增加、环状染色体的不稳定性以及不同核型嵌合比例不同等密切相关。本例患者临床表现与其复杂的染色体嵌合核型有关,对此类患者的后期临床应密切关注。     

1例18号环状嵌合体的遗传学分析

目的 通过对1例身材矮小、特殊面容、智力低下的患儿进行细胞遗传学检查,探究其临床表现与遗传学因素的关系,并分析其影响因素。方法 对患儿进行外周血G显带染色体核型分析和染色体微阵列芯片检测。结果 染色体核型分析结果为46,XX,r(18)(p11.3q23)[70]/46,XX,der(18)r(18;18)(p11.3q23;p11.3q23)[14]/45,XX,-18[6],染色体微阵列芯片检测结果显示18q22.3q23存在大小约7.799 Mb的拷贝数缺失。结论 本例患儿的临床表现主要与18号染色体长臂末端缺失及环状染色体的不稳定性有关。     

一例新发生的5p部分单体合并隐匿18p微小重复

目的 对1例临床表型严重的疑似猫叫综合征患者的核型进行确诊,为评估该家庭的再发风险提供依据.方法 采用高分辨G-显带核型分析患者及其父母,应用猫叫综合征关键区基因位点特异性探针(5p15.2,D5S23/D5S721)、Tel 5p/5q、Tel 18p/18q亚端着丝粒探针和18号染色体涂染探针进行荧光原位杂交(fluorescence in situ hybridization,FISH)检测患者及其父母,SNP-Array对患者全基因组DNA进行扫描分析.结果 高分辨G-显带核型分析发现患者5p末端有微小缺失.应用猫叫综合征关键区基因位点特异性探针荧光原位杂交结果发现患者D5S23/D5S721位点缺失.高密度的SNP-Array芯片检测结果显示该患者5号染色体短臂末端存在15 Mb片段的缺失合并18号染色体短臂末端存在约2 Mb的重复.应用5p亚端着丝粒探针和18p亚端粒探针进行FISH进一步确定了患者携带一条源于5p和18p易位而来衍生的5号染色体.最终确定其染色体核型为46,XY,der(5)t(5;18)(p15.1;p11.31)dn.结论 SNP-Array结合FISH技术确诊了患者为新发生的5p部分缺失合并隐匿的18p部分重复,在其家庭复发风险低.SNP-Array能检出微细的染色体不平衡改变,对于染色体的病因学分析及复发风险评估具有重要价值.     

“5p+”猫叫综合征的遗传学分析

猫叫综合征是5号染色体短臂缺失,又称5p-综合征。由于该病患儿哭声似猫叫而得名。本文对具有猫叫综合征临床特征的患儿及父母做外周血染色体检测,并对其5p+进行遗传学分析如下。资料与方法1.病例资料患儿,女,18天,第2胎第2产,36周早产。该患儿哭声似猫叫,眼距宽,耳位低,小下颌,枕骨突出。其父母非近亲婚配,第1胎孕8个月生后死亡。2.方法取患儿及其父母外周血,72hr淋巴细胞培养,常规制片,G显带,进行核型分析。图1 003患儿核型:46,XX,5p+;004患儿母亲核型:46,XX,t(5;7)(p15.1;q32)结果患儿核型为46,XX,5p+;其父核型正常为46,XY;其母核型为46,XX,t(5;7)(p15.1;q32),见图1。讨论猫叫综合征是由于5号染色体短臂缺失所引起的一种较为罕见的染色体病,是常染色体结构畸变所致疾病中较常见的一种。新生儿发病率为1/50000[1]。高调的猫叫样哭声是该病具有诊断意义的特征。该综合征,大部分为新的突变,只有10%-15%源自平衡易位的亲本。本例患儿5号染色体的异常来自于平衡易位的母亲,其母7号染色体长臂q32及5号短臂p15.1处断裂后相互易位,易位后的5...     

一例嵌合型环状13号染色体病例报道和文献回顾

13号环状染色体综合征临床中通常表现为发育迟缓或智力低下等先天异常。本文报道了1位由于嵌合型13号环状染色体造成的智力低下的5岁女童。患儿外周血染色体核型分析为mos 46,XX[35]//45,XX,-13[10]/45,XX,t(13;13)(p13q34)[12]/46,XY,r(13)(p13q34)[22]/46,XX,del(13)(q31-qter)[13]。我们比较本病例与国外报道的r(13)(p13q34)型环状13号染色体综合征临床特征,提示13号环状染色体综合征患者临床特征有很大的变化。     

一例45,XX,-13/46,XX,r(13)/46,XX,r(13;13)/47,XX,2r(13)(p13q32.3)患者及其表型定位研究

目的　通过对 1例 13号环状染色体综合征患者的染色体分析、表型定位研究和相关文献复习比较 ,探索染色体区带与表型的关系。方法　应用染色体G带、C带、N带、高分辨显带技术、表型定位和文献复习比较分析方法 ,对 1例 13号环状染色体综合征患者进行了研究。结果　患儿双亲核型正常 ,患儿核型为 45 ,XX ,-13 /4 6,XX ,r( 13 ) /4 6,XX ,r( 13 ;13 ) /4 7,XX ,2r( 13 ) ( p13q3 2 .3 ) ;典型的 13号环状染色体综合征与 13q3 4的缺失相关 ;13号环状染色体综合征患者的手足、肾脏、骨骼、外生殖器异常及心脏杂音与 13 q3 2 q3 2 .2片段的缺失有关 ,缩颌与 13q3 2 .3 q3 3片段的缺失相关 ,肛门闭锁与 13 q2 2 q3 2的缺失相关 ,无脑畸形与 13 q13 q2 2片段的缺失相关。 结论　新的环状染色体断裂重接点在 13 p13和 13q3 2 .3 ;13号环状染色体综合征患者临床特征的差异与染色体区带缺失部位的不同密切相关。     

一例环状X染色体嵌合体Turner综合征的双色荧光原位杂交

目的通过对1例环状X染色体嵌合体的细胞遗传学分析，探讨环状X染色体形成的原因，临床表现与染色体核型的关系。方法应用染色体G显带技术对环状染色体进行识别，并选用DXZ1和DYZ3探针，通过双色荧光原位杂交技术进一步确认环状染色体来源。结果患儿染色体核型为45，X[83]／46，X，r（X）（p22．1q22）[16]／47，X，2r（X；X）（p22．1q22；p22．1q22）[1]。双色荧光原位杂交示ish（DYZ3-）r（x）（DXZ1＋）。结论具X染色体大环的染色体核型非常罕见，Turner综合征患者的临床表型和染色体核型存在依赖性，对于青春前期身材矮小的女性患儿应高度警惕X染色体的异常。     

慢粒患者经格列卫治疗后细胞遗传学改变:标准Ph易位t(9;22)(q34;q11)变为变异Ph易位t(21;22)(p11;q11)

目的通过对慢性粒细胞白血病(chronic myeloid leukemia,CML)患者经格列卫药物治疗后细胞遗传学改变的研究,探讨ABL-BCR的表达缺失与获得性格列卫耐药的关系。方法应用R显带技术对染色体进行核型分析,并选用BCR/ABL探针,通过双色荧光原位杂交技术进一步确认遗传学分析。结果患者经格列卫治疗后染色体核型由t(9;22)(q34;q11)变为t(21;22)(p11;q11)。双色荧光原位杂交证实此患者核型应为46,XY,t(9;22;21)(q34;q11;p11)。结论变异Ph易位中ABL-BCR的表达缺失与获得性格列卫耐药有关,荧光原位杂交技术在检测变异易位中起重要作用。     

一例伴t(14;14)(q11;q32)易位的B细胞急性淋巴细胞白血病的临床和分子细胞遗传学研究

目的 报告1例伴t(14;14)(q11;q32)易位的罕见B细胞急性淋巴细胞白血病(B-lineage acute lymphoblastie leukemia,B-ALL)病例,阐明其临床和分子细胞遗传学特征.方法 分析1例伴t(14;14)(q11;q32)易位B-ALL患者的临床资料;将患者骨髓细胞24h培养后按常规方法制备染色体标本,采用R显带技术进行核型分析;分别应用IGH双色断裂点分离探针、CEBPE双色断裂点分离探针、4号全染色体涂染探针和ALL组合探针进行荧光原位杂交(fluorescence in situ hybridization,FISH)分析.结果 常规细胞遗传学分析显示患者核型为47,XX,+4,t(14;14)(q11;q32)[20],FISH分析进一步证实了这种核型异常.IGH双色断裂点分离探针FISH分析表明t(14;14)(q11;q32)易位累及IGH基因,CEBPE双色断裂点分离探针FISH分析提示t(14;14)(q11;q32)易位中IGH的伙伴基因为CEBPE基因.结论 在B-ALL中t(14;4)(q11;q32)易位同时累及IGH和CEBPE基因为少见的再现性遗传学异常,该异常可定义B-ALL中一种新的亚型.伴有t(14;14)(q11;q32) IGH/CEBPE易位的B-ALL患者可能预后较好.     

一例21号环状染色体综合征的细胞遗传学和表型定位分析

目的通过对1例21号环状染色体综合征患者的细胞遗传学分析，探讨21号环状染色体的形成原因，临床表型与染色体区带的关系。方法应用染色体G带、C带、N带、高分辨显带和荧光原位杂交技术对21号环状染色体进行识别与定位。结果患儿双亲核型正常，患儿核型为46，XY，r（21）[91]／46，XY，r（21；21）（p11q22．3；p11q22．3）[5]／45，XY，-21[4]。结论21号环状染色体综合征的临床表现与21q末端缺失的多少相关，男性性别发育异常可能与21q22．3片段的缺失相关。     

Ring chromosome 9 [r(9)(p24q34)]: a report of two cases

We report clinical and molecular cytogenetic studies in two patients with ring chromosome 9. Cytogenetics and fluorescent in situ hybridization (FISH) analysis using the p16 gene probe on 9p21, the ABL gene on 9q34, chromosome 9 alpha satellite-centromeric probes, and TelVision 9p and 9q probes which identify subtelomere-specific sequences on chromosome 9p and 9q, revealed 46,XX,r(9)(p24q34).ish r(9)(305J7-T7-,p16+,ABL+, D9S325-) and 46XY,r(9)(p24q34).ish r(9)(305J7-T7-,p16+,ABL+, D9S325-). Based on FISH analysis at least 115 kb was deleted on terminal 9p, and at least 95 kb from terminal 9q. In comparison with other reports of r(9), deletion 9p, and deletion 9q, both patients had clinical characteristics of ring 9 and additional features of deletion 9q or deletion 9p syndrome. The variability between the two cases with r(9) despite similar breakpoints identified by GTG-banding and FISH may be explained by submicroscopic differences between deletion breakpoints, ring instability, interaction of other genes on the phenotype, and variation in fetal environmental conditions.     

Clinical and molecular‐cytogenetic studies in seven patients with ring chromosome 18

We report the results of detailed clinical and molecular‐cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non‐mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18–specific short‐arm paint, centromeric, subtelomeric, and a panel of fifteen Alu‐ and DOP‐PCR YAC probes. The breakpoints were assessed with an average resolution of ∼2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 (∼35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter→p11.32::q21.3→qter) and inv dup(18)(qter→p11.32::p11.32→p11.1: :q21.3→qter)pat, with no evidence of an 18p deletion. A novel inter‐intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of “ring instability syndrome” cannot be excluded, the phenotypes of our patients with characteristic features of 18q‐ and 18p‐ syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome. © 2001 Wiley‐Liss, Inc.     

Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18.

We report the results of detailed clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18-specific short-arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-PCR YAC probes. The breakpoints were assessed with an average resolution of approximately 2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 ( approximately 35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter-->p11.32::q21.3-->qter) and inv dup(18)(qter-->p11.32::p11.32-->p11.1: :q21.3-->qter)pat, with no evidence of an 18p deletion. A novel inter-intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18p- syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome.     

Delineation of the dup5q phenotype by molecular cytogenetic analysis in a patient with dup5q/del 5p (cri du chat)

An infant girl presented with multiple congenital abnormalities and a distinctive mewing cry. Her karyotype was 46,XX,add5p. Chromosome analysis on the mother revealed an apparently balanced pericentric inversion of chromosome 5, with the precise position of the breakpoints not clearly discernable by GTG banding, 46,XX,inv(5)(p15.2/3?q35.1?). Fluorescence in situ hybridization (FISH) studies using a commercial cri du chat probe (D5S721,D5S23) revealed signals on both the normal and derivative chromosomes. Telomeric probes specific for 5p and 5q were used to confirm the pericentric inversion in the mother and demonstrated the loss of the terminal 5p region and a duplication of the terminal 5q region in the proband. The imbalance on chromosome 5 in the patient was further defined using comparative genomic hybridization (CGH), which revealed a loss of material from 5p15.3 --> pter and a gain of 5q34 --> qter. The presence of the cat-like cry appears to be the only specific feature that can be linked to the loss of 5p material. The remaining dysmorphic features of this infant appear to be due specifically to the duplication of the 5q sequences. The combination of FISH, CGH, and cytogenetics has confirmed that the characteristic cry of the cri du chat syndrome is due to the deletion of the most distal part of the classic del 5p region. More importantly, our investigation has defined the duplication of 5q34 --> qter as a distinct clinical phenotype.     

Familial complex chromosome rearrangement giving rise to balanced and unbalanced recombination products

We report on a family ascertained through a 14-month-old girl with a terminal deletion of chromosome 8p23.1. Analysis of the karyotype of other relatives showed that the mother is the carrier of a balanced complex 4-break chromosome rearrangement, which she and her brother inherited from their father following recombination. This complex chromosome rearrangement (CCR) was confirmed by fluorescence in-situ hybridization (FISH) using libraries for chromosomes 1, 8, and 9, and telomeric probes for the long arm of chromosome 9. The karyotype of the maternal grandfather was 46,XY,t(1;8) (p31;q21.1),t(8;9)(p23.1;q34). The karyotype of his daughter is 46,XX,rec(8)t(1;8) (p31;q21.1)t(8;9)(p23.1;q34)pat. The karyotype of the proposita is 46,XX,rec(8)t(8;9) (p23.1;q34)mat, and that of her abnormal elder sister is 46,XX,t(1;8)(p31;q21.1)rec(8) t(8;9)(p23.1;q34)mat,der(9)t(8;9)(p23.1;q34) mat. Unbalanced segregation and/or recombination during maternal meiosis gave rise to the two abnormal sisters, one effectively with 8p trisomy and the other with monosomy for that same 8p segment. To our knowledge, this is the first case of a familial CCR giving rise to unbalanced recombination products. Am. J. Med. Genet. 79:30–34, 1998. © 1998 Wiley-Liss, Inc.     

Clinical, cytogenetic, and fluorescence in situ hybridization findings in two cases of "complete ring" syndrome

The term "ring syndrome" was proposed to describe a phenotype of growth failure without major malformations due to a ring autosome. The growth failure is thought to be caused by instability of the ring chromosome leading to aneusomy and cell death. Most previous studies of ring chromosomes were based on standard cytogenetic banding techniques and were limited to microscopically detectable deletions in the ring chromosomes. We report on two patients with complete ring (4) and ring (9) chromosomes, respectively. The first was a 15-month-old girl and the second was a 16-month-old boy. They both presented with severe, symmetrical growth failure and normal psychomotor development in the absence of malformations. Their parents had a normal phenotype. The first case had a whorled pattern of hyperpigmentation and hypopigmentation on part of the face and chest, and the second case had a patchy hyperpigmented rash on the trunk. Peripheral blood karyotype of the first patient was 46,XX, r(4)(p16.3q35.2) and of the second 45,XY,-9/46,XY,r(9)(p24q34.3). G-band analysis suggested no loss of material in the ring chromosomes. These findings were confirmed by fluorescence in situ hybridization (FISH) analysis using chromosome-specific subtelomeric probes. The common human telomeric sequences were intact in the first patient but absent in the second patient. The cytogenetic and FISH data in our two cases provide further evidence for the existence of a "complete ring" phenotype independent of the autosome involved. Pigmentary skin changes are a useful clinical sign of mosaicism caused by the ring instability.     

Unbalanced translocation,t(18;21), detected by fluorescence in situ hybridization (FISH) in a child with 18q– syndrome and a ring chromosome 21

We report on an 8-year-old girl with minor anomalies consistent with 18q-syndrome and mild developmental delay. Initially cytogenetics showed a terminal deletion of chromosome 21 with mosaicism for a small ring chromosome 21 as the only apparent karyotypic abnormality: mos 45,XX,-21/46,XX,+r(21) (48%/52%). Further studies including FISH and DNA analysis demonstrated a denovo unbalanced translocation of chromosomes 18 and 21 with the likely breakpoints in 18q23 and 21q21.1. Most of 21q was translocated to the distal long arm of one chromosome 18, and this derivative 18 appeared to lack 18q23-qter. The small ring chromosome 21 [r(21)], present in only 52% of the patient's blood lymphocytes, did not appear to be associated with the abnormal phenotype since all 13 chromosome 21 markers that were examined in genomic DNA were present in 2 copies, and the phenotype of the patient was consistent with the 18q – syndrome. The Karyotype was reinterpreted as mos 45,XX,–18,–21,+der(18) t(18;21) (q23;q21.1)/46,XX, –18, –21,+der(18) t(18;21) (q23;q21.1), +r(21) (p13q21.1) (48%/52%). These results demonstrate the power of FISH in conjunction with DNA analysis for examination of chromosome rearrangements that may be misclassified by traditional cytogenetic studies alone. © 1993 Wiley-Liss, Inc.     

Characterization of a de novo 48,XX, + r(X), + r(17) by in situ hybridizatio in a patient with neurofibromatosis (NF1)

We describe a patient with familial neurofibromatosis (NF1), short stature, developmental delay, and a de novo chromosome abnormality. In sity hybridization was done using chromosome specific centromere probes to characterize the karyotype as 46,XX/47, XX,+r(X) (p11q11)/47,XX,+r(17) (p11q11)/48, XX,+r(X) (p11q11),+r(17) (p11q11). The NF1 mutation, as well as each superunmerary ring chromosome, may have played a role in perturbing the normal developmenal process of this patient. © 1993 Wiley-Liss, Inc.     

Array-based comparative genomic hybridization facilitates identification of breakpoints of a novel der(1)t(1;18)(p36.3;q23)dn in a child presenting with mental retardation

Monosomy of distal 1p36 represents the most common terminal deletion in humans and results in one of the most frequently diagnosed mental retardation syndromes. This deletion is considered a contiguous gene deletion syndrome, and has been shown to vary in deletion sizes that contribute to the spectrum of phenotypic anomalies seen in patients with monosomy 1p36. We report on an 8-year-old female with characteristics of the monosomy 1p36 syndrome who demonstrated a novel der(1)t(1;18)(p36.3;q23). Initial G-banded karyotype analysis revealed a deleted chromosome 1, with a breakpoint within 1p36.3. Subsequent FISH and array-based comparative genomic hybridization not only confirmed and partially characterized the deletion of chromosome 1p36.3, but also uncovered distal trisomy for 18q23. In this patient, the duplicated 18q23 is translocated onto the deleted 1p36.3 region, suggesting telomere capture. Molecular characterization of this novel der(1)t(1;18)(p36.3;q23), guided by our clinical array-comparative genomic hybridization, demonstrated a 3.2 Mb terminal deletion of chromosome 1p36.3 and a 200 kb duplication of 18q23 onto the deleted 1p36.3, presumably stabilizing the deleted chromosome 1. DNA sequence analysis around the breakpoints demonstrated no homology, and therefore this telomere capture of distal 18q is apparently the result of a non-homologous recombination. Partial trisomy for 18q23 has not been previously reported. The importance of mapping the breakpoints of all balanced and unbalanced translocations found in the clinical laboratory, when phenotypic abnormalities are found, is discussed.     

Meiotic origin of two ring chromosomes 18 in a girl with developmental delay

We report on the cytogenetic, fluorescence in situ hybridization (FISH), and molecular results obtained for a patient with a mild and nonspecific pattern of minor anomalies and developmental delay. In the proband's karyotype one chromosome 18 was replaced by a ring chromosome 18 in all metaphases, with deletion of the terminal regions. Furthermore, 56% of the metaphases contained a supernumerary small ring chromosome. Microdissection followed by FISH analysis demonstrated that the small ring chromosome consisted of material from the pericentromeric region of chromosome 18. The karyotype was defined as 46,XX,r(18)(p11.3q23)[88]/47,XX,r(18)(p11.3q23)+r(18)(p11.22q12.2)[112]. Thus, the patient has a deletion at 18pter and at 18qter, and a mosaic partial trisomy of the pericentromeric region of chromosome 18. We undertook molecular analysis using DNA samples of the patient and her parents in order to clarify the origin and possible mode of formation of the chromosome abnormalities. Our results show a paternal origin of the structurally normal chromosome 18 and a maternal origin for both ring chromosomes 18. Interestingly, the smaller ring chromosome did not arise postzygotically from the larger ring, since the two ring chromosomes contain genetic material derived from the two different maternal chromosomes 18. The abnormalities appear to have arisen during a meiotic division, and it could be speculated that both ring chromosomes 18 arose simultaneously due to complex pairing and recombination events. After fertilization, the small ring chromosome was lost in a subset of cells, thus leading to mosaicism.