21号环状染色体的细胞遗传学分析

目的通过对1例21号环状染色体嵌合体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及嵌合比例的关系。方法应用染色体常规标本、G显带、C显带技术对21号环状染色体进行识别与区带定位。结果患者核型为mos46,XX,r（21）（pllq22）[91]／45,XX,-21[5]／46,XX,dicr（21;21）（pllq22;p11q22）[4]。结论环状染色体断裂位点在21pll和q22,21号环状染色体综合征的临床表现与核型嵌合比例及21q末端缺失的多少相关,女性不孕可能与21q22片段的缺失相关。     

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。     

5例环状染色体综合征的产前诊断和表型分析

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。     

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。     

嵌合型4号环状染色体患儿1例的遗传学分析

目的探讨1例嵌合型4号环状染色体患儿核型的成因、临床表型及发病机制。方法选取2020年2月15日于滕州市妇幼保健院就诊的1例嵌合型4号环状染色体患儿为研究对象。收集患儿的临床资料, 对其进行外周血染色体G显带核型分析、染色体微阵列分析(CMA)、荧光原位杂交(FISH)检测, 并对文献进行回顾。结果患儿为足月小样低体重儿, 具有特殊面容、动脉导管未闭、室间隔缺损。外周血染色体核型为mos 46, XY, r(4)(p16.3q35.2)[259]/45, XY, -4[25]/47, XY, r(4)(p16.3q35.2), +r(4)(p16.3q35.2)[8]/46, XY, der(4)del(4)(p16.3)inv(4)(p16.3q31.1)[6]/46, XY, dic?r(4;4)(p16.3q35.2;p16.3q35.2)[4]/48, XY, r(4)(p16.3q35.2), +r(4)(p16.3q35.2)×2[3]/46, XY, r(4)(p1?q2?)[2];CMA检测结果为arr[GRCh37]4p16.3(68 345-2 981 614)×1...     

一例3p26．3-pter缺失及7q31．33-qter重复患儿的临床表型与遗传学分析CSCD

目的明确1例发育落后合并多发畸形患儿染色体拷贝数变异（copy numbervariants,CNVs）的性质及来源,并分析其与表型的相关性。方法应用常规G显带分析患儿及其父母的外周血染色体核型,应用二代测序（next generation sequencing,NGS）技术对患儿进行检测。结果G显带分析显示患儿的3号染色体存在结构异常,其父亲的染色体核型为46,XY,t（3;7）（p26;q31）,其母亲核型未见异常。NGS检测显示患儿染色体3p26．3-pter区存在约2．16Mb的微缺失,7q31．33-qter区存在约34．24Mb的重复。结论患儿3号染色体的结构异常源自其父亲的t（3;7）平衡易位,其核型为46,XY,der（3）t（3;7）（p26．3;q31．33）pat。3p26．3-pter区微缺失和7q31．33-qter区重复是导致患儿异常表型的原因。     

96例Turner综合征患者临床特征及染色体分析

目的Turner综合征患者身材矮小伴不同程度的性腺发育不全,探讨Turner综合征不同核型的遗传学特征、临床特点及其所占比例。方法无菌取患者外周血,淋巴细胞常规培养制作染色体标本,胰酶法G显带,显微镜下进行染色体核型分析。结果96例Turner综合征患者的染色体核型为：45,x,39例（40．6％）;45,Ⅺ／46,XX21例（21．9％）;46,XY11例（11．5％）;46,Xi（Xq）10例（10．4％）;46,X,del（x）（q22。qter）6例（6．3％）;45,X／46,Xi（X）（q10;q10）3例（3．1％）;47,XXX3例（3．1％）;45,X／46,X,del（X）（022—pter）2例（2．1％）;45,Ⅺ／46,X,r（X）（p22q28）1例（1．04％）。结论Turner综合征患者的染色体有数目异常和结构畸变等多种核型,均可不同程度导致女性闭经、性腺发育异常及智力低下等症状,应提倡优生优育,做好产前诊断。     

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。     

21号环状染色体嵌合体胎儿2例的临床特征和遗传学分析

目的探讨2例21号环状染色体嵌合体胎儿的围产期临床表型和遗传学特征。方法选取2021年11月在厦门市妇幼保健院接受介入性产前诊断的2例胎儿为研究对象。收集2例胎儿的临床资料, 应用常规G显带核型分析和染色体微阵列分析(CMA)对2例胎儿及其父母进行遗传学检测。结果胎儿1超声提示胎儿鼻骨未显示、室间隔缺损、永存左上腔静脉、三尖瓣轻度返流, 染色体核型结果为46, X?, dic r(21;21)(p12q22;q22p12)[41]/45, X?, -21[9], CMA检测结果提示其染色体21q11.2q22.3区存在30.00 Mb片段的4拷贝, 21q22.3区存在3.00 Mb片段的缺失。胎儿2超声提示鼻骨呈点状回声, 核型为46, X?, r(21)(p12q22)[83]/45, X?, -21[14]/46, X?, dic r(21;21)(p12q22;q22p12)[3], CMA结果提示其染色体21q22.12q22.3区存在5.10 Mb片段的4拷贝, 21q22.3区存在2.30 Mb片段的缺失。结论 2例21号环状染色体嵌合体的围产期表型与靠近染色体缺失断裂位...     

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。     

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.     

Monosomy 8 rescue gave cells with a normal karyotype in a mildly affected man with 46,XY,r(8) mosaicism

The psychomotor and somatic development from early childhood into adult life is described in a man with 46,XY,r(8)/46,XY mosaicism. The ring chromosome 8 appeared to be of normal length on G-banding, but terminal deletions on 8q and 8p were detected with FISH and CGH. By STR marker analysis the 8p deletion proved to be quite large, at least 6.74 Mb, while the 8q deletion was small, around 2.5 Mb. The haplotype analysis also demonstrated that the r(8) originated from a maternal chromosome 8, and that cells with normal male karyotype resulted from monosomy 8 rescue after loss of the ring 8, i.e. a mitotic duplication of the paternal chromosome 8. The patient has a mild phenotype with no malformations and mild mental retardation, also compared to other ring chromosome 8 patients. His clinical condition has remained stable for the last 20 years.     

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.     

Duplication of 7p21.2→pter due to maternal 7p;21q translocation: Implications for critical segment assignment in the 7p duplication syndrome

We describe a 1-year-old boy with mental and physical retardation, a large anterior fontanel, brachycephaly with flat occiput, short and stubby fingers, generalized hypotonia, ocular hypertelorism, low-nasal bridge, long philtrum, high-narrow palate, apparently low-set ears, and a small mandible. Cytogenetic analysis utilizing high resolution chromosome banding technique showed an unbalanced karyotype consisting of 46,XY,add(21)(q22.3) that originated from maternal balanced translocation between chromosomes 7 and 21. Fluorescence in situ hybridization (FISH) using micro-dissected library probe pool from chro-mosome 7 confirmed the additional material on 21q was derived from chromosome 7. Our results indicated that the patient had an unbalanced translocation, 46,XY,der(21)t(7;21)(p21.2;q22.3)mat, which resulted in duplication for distal 7p. Our patient is similar to reported cases with a 7p15→pter or larger duplication of 7p, suggesting that the critical segment causing the characteristic phenotype of 7p duplication syndrome, including large anterior fontanel, exists at 7p21.2 or 7p21.2→pter. Am. J. Med. Genet. 86:305–311, 1999. © 1999 Wiley-Liss, Inc.     

Two cases of ring chromosome 11.

Two cases of ring chromosome 11 are reported. Both had mental retardation, microcephaly, and short stature. High resolution G banding in case 1 showed no visible loss of chromatin, the karyotype being assessed as 46,XX,r(11) (p15 X 4q2 X 5). In case 2, a Wilm's tumour developed at 8 months and the child died at 18 months. Cytogenetic analysis by Q banding demonstrated minimal chromosome deletion and the karyotype was considered to be 46,XY,r(11) (p15q25).     

Apparent monosomy 21 owing to a ring 21 chromosome: parental origin revealed by DNA analysis.

A three and a half year old mildly retarded boy is presented. Karyotyping showed monosomy 21 (45,XY,-21) in all 50 metaphase spreads examined from two lymphocyte cultures, and in 20% of cells examined from cultured fibroblasts; the remaining 80% of cells showed a ring 21 chromosome (46,XY,r(21)(p1q22]. Molecular studies using chromosome 21 specific DNA probes confirmed the monosomy in blood and showed that the ring 21 chromosome was paternal in origin. Parental karyotypes were normal.     

9号环状染色体综合征的荧光原位杂交分析

目的 对1例9号环状染色体综合征患儿进行细胞分子遗传学分析,探索9号环状染色体与临床表型的关系.方法 采用染色体G显带核型分析和TelVision 9p探针和TelVision 9q探针进行双色荧光原位杂交,识别和定位1例9号环状染色体患儿.结果 患儿核型为45,X,-9/46,XX,r(9)(p24q34)/46,XX,r(9;9)(p24q34;p24q34)(4/92/4).双色荧光原位杂交显示9号环状染色体上没有杂交信号,提示9号环状染色体短臂末端缺失片段至少有115 kb,长臂末端缺失片段至少有95 kb.与其它报道的环状9号染色体综合征、9号染色体短臂和长臂部分单体综合征相比,本例患者兼有环状9号染色体综合征的临床特征以及9号染色体短臂和长臂部分单体综合征的一些特征.结论 由于缺失的断裂点之间亚显微结构的不同、环的不稳定性、基因与表型相互作用以及胎儿环境条件的不同等原因,具有相同断裂点的9号环状染色体综合征患者可以有不同的临床表型,单倍基因剂量不足对临床表型发挥了重大作用.     

Ring chromosome 21 in a boy and a derivative chromosome 21 in the mother: implication for ring chromosome formation

We report on r(21) chromosome in a boy and a der(21) chromosome in his mother. Cytogenetic studies revealed a mosaic 45,XY[4]/46,XY,r(21)[96] karyotype in the boy and a 46,XX,der(21)[100] karyotype in the mother. Fluorescence in situ hybridization analysis for D21Z1 at the centromere, AML1 at 21q22.1, LSI21 at 21q22.2, and 21qtel at the telomere region showed that the r(21) chromosome retained single copies of D21Z1, AML1, and LSI21 and lacked the 21qtel, whereas the der(21) chromosome had two copies of the 21qtel on both of its ends and single copies of D21Z1, AML1, and LSI21, with a paracentric inversion of AML1 and LSI21 (21qtel-D21Z1-LSI21-AML1-21qtel). Microsatellite analysis for nine loci on 21q22.3 indicated that the r(21) chromosome was missing a distal 21q22.3 region involving D21S1890, D21S1411, and D21S1903 with no maternally derived alleles, and that the der(21) chromosome was associated with duplication of a distal 21q22.3 region encompassing D21S1890 and D21S1446. The results suggest that a U-type exchange occurred between the homologous distal 21q regions duplicated on the der(21) chromosome, leading to the r(21) formation. This is a novel mechanism put forward for the formation of a monocentric ring chromosome.