染色体核型高度复杂异常一例

目的探讨骨髓增生异常综合征(MDS)患者伴有高度复杂异常染色体的临床特点。方法报道1例骨髓增生异常综合征转化为急性白血病,并观察此类患者骨髓造血细胞病态造血、染色体核型异常与患者生存期的关系。结果患者全血细胞减少,肝脾肿大,伴有肾功能衰竭,西安金域医学检验公司染色体核型分析:48,XX,del(5)(q13q31),+8,+13 del(13)(q32),-20,marl[5]/48,XX,+10,-20,+marl×2[4]/46,XX[1];骨髓活检示:1免疫组化:CD34小血管(+),圆核细胞散在少(+),CD61巨核细胞多(+),可见单圆核及淋巴样巨核细胞;2结合免疫组化,网染(++)符合骨髓增生异常综合征;患者于确诊骨髓增生异常综合征后3个月转化为急性髓系白血病,由于患者及家属拒绝化疗,出现多次交叉配血不合,无法行输血支持治疗,自动出院后2周内死亡。结论高度复杂异常染色体患者转为急性白血病速度快、生存期短,预后极差。     

染色体异常核型32例细胞遗传学分析

采用外周血淋巴细胞培养、染色体制片、G显带分析方法探讨各类异常染色体畸变与其表型效应关系。结果436例患者中检出32例染色体异常核型,异常检出率为7.3%;其中性染色体数目异常11例(34.4%),嵌合型4例(12.5%),结构异常5例(15.6%);男性反转综合征1例(3.1%);常染色体数目异常1例(3.1%),结构异常10例(31.3%)。性染色体异常患者表现为不同程度的性腺发育不良和体格发育异常,常染色体异常患者均有不育、流产、死胎或畸胎史。凡有不良妊娠史的夫妇、闭经或性腺发育不良的患者,进行细胞遗传学分析,可确定病因和类型,为治疗提供依据。     

360例体貌异常儿童染色体核型分析

染色体病是一种严重危害人类健康、影响人口质量的遗传病，在新生儿中约0．8％的人患染色体病。而患染色体病者，往往有特殊的体貌，为探讨体貌异常儿童临床表现与外周淋巴细胞染色体异常核型关系，我科对近几年来院就诊的360例体貌异常患儿进行外周血淋巴细胞染色体检查，现报告如下：     

1例12号环状染色体的遗传学分析

目的探讨1例患有12号环状染色体患者的临床表型和遗传学特征。方法收集1例12号环状染色体患者的症状、体征和影像学检查等临床资料,应用染色体常规G显带技术(chromosome G banding technique)、染色体微阵列分析(chromosomal microarray analysis,CMA)、荧光原位杂交(Fluorescence in situ hybridization,FISH)和多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)进行分析。结果本例12号环状染色体患者流产2次,其他临床体征正常;性激素6项正常;抗苗缪勒管激素0.57 ng/m L,低于参考区间;腹部B超未见异常;该患者核型为mos 46,XX,r(12)(p13q24)[96]/45,XX,-12 [3]/46,XX,dic r(12; 12)(p13q24)[1]; CMA结果显示12号染色体在12q24.33区域存在小片段的缺失,缺失区域为良性CNVs; FISH检查结果显示12号环状染色体长臂末端缺失; MLPA检查结果显示12号长臂末端亚端粒缺失。结论本例环状12号染色体临床体征正常,环状染色体的临床表现与核型嵌合比例及12q末端缺失的多少相关,女性流产可能与r(12)的不稳定相关。     

187例介入性产前诊断双胎的染色体核型和染色体微阵列结果分析

目的探讨染色体核型分析和染色体微阵列分析(CMA)对于双胎妊娠的产前诊断价值。方法回顾性分析187例产前诊断双胎孕妇(374个胎儿)的染色体G显带和染色体微阵列检测结果。结果 374个胎儿染色体G显带分析结果共检出31个异常核型胎儿(8.29%,31/374)。异常核型中数目异常19个(61.29%,19/31);嵌合体4个(12.90%,4/31);结构异常10个(32.26%,10/31)。374个胎儿染色体微阵列分析结果中,异常结果有36例(9.63%,36/374)。36个异常结果中数目异常18个(50%,18/36),嵌合体异常3个(8.33%,4/36),结构异常15个(41.67%,15/36)。在染色体核型正常的343个胎儿中,共检出CMA异常胎儿11个,额外检出率为3.21%(11/343)。联合两种检测方法结果,374个胎儿中共检测出异常胎儿42个,总异常率11.23%(42/374)。结论对于有指征的双胎孕妇,应更严格地进行介入性产前诊断,建议其同时联合染色体核型和染色体微阵列检测,减少出生缺陷的发生。     

25例伴复杂变异易位的慢性粒细胞白血病细胞遗传学分析

慢性粒细胞白血病（CML）是起源于多能干细胞的恶性血液病.染色体核型分析对CML的诊断、预后和发病机制的探讨都具有重要的价值.Ph染色体是CML的标志性染色体,95%的CML有该染色体.约5%CML可有变异的Ph染色体,形态上将其分为简单型和复杂型.迄今文献中已报道伴变异易位的CML逾300例.国内亦有相关报道.但对伴复杂变异易位的CML报道不多.现将我院近十年来伴复杂变异易位的25例CML患者的分析结果报告如下.     

166例生殖系统发育异常患儿的细胞遗传学分析

本文对我室166例生殖系统发育异常患儿进行了外周血染色体分析，试图分析生殖系统发育异常患儿染色体畸变特点。患儿均来自我院外科及儿科门诊，年龄在12天～16岁，临床表现以外生殖器发育异常而就诊，患儿均经过常规查体，染色体核型分析，内分泌检测等检查。染色体检查结果。正常核型144例，其中46，XY112例，占67．46％，46，XX32例，占19．27％，异常核型者22例，占13．25％。提示：对生殖系统发育异常患儿，应利用细胞遗传学和分子遗传学检测手段，及早诊断，合理治疗。     

Prenatal genetic diagnosis of omphalocele by karyotyping,chromosomal microarray analysis and exome sequencing

ObjectivesThe aim of this study is to share our experience in the prenatal diagnosis of omphalocele by karyotyping, chromosomal microarray analysis (CMA) and whole exome sequencing (WES).MethodsIn this retrospective study, 81 cases of omphalocele were identified from 2015 to 2020. Associated anomalies and prenatal diagnosis based on karyotyping, CMA and WES were analysed.ResultsFifty-eight (71.6%) of the 81 foetuses had other ultrasound anomalies. Giant omphalocele was present in 11 cases (13.6%) and small omphalocele was present in 70 cases (86.4%). Chromosomal abnormalities were found in 24 foetuses (29.6%, 24/81), the most common of which were trisomy 18 (58.8%, 11/24) and trisomy 13 (29.2%, 7/24). Compared to isolated omphalocele, non-isolated omphalocele was accompanied by an increased prevalence of chromosomal abnormalities (4.3% (1/23) vs. 39.7% (23/58), χ² = 8.226, p = .004). All chromosomal abnormalities were found in small omphalocele. Aside from aneuploidy, CMA showed one pathogenic copy number variants (CNVs) for a detection rate of 1.2%, one variants of unknown significance (VOUS) and one instance of loss of heterozygosity (LOH). WES was performed on 3 non-isolated cases, and one was found to have pathogenic variants.ConclusionsThe most common genetic cause of omphalocele is aneuploidy and the prevalence of chromosomal abnormalities is increased with non-isolated and small omphalocele. CMA and WES can be useful for providing further genetic information to assist in prenatal counselling and pregnancy management.     

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

BackgroundCorpus callosum abnormality (CCA) can lead to epilepsy, moderate severe neurologic or mental retardation. The prognosis of CCA is closely related to genetic etiology. However, copy number variations (CNVs) associated with fetal CCA are still limited and need to be further identified. Only a few scattered cases have been reported to diagnose CCA by whole exome sequencing (WES).MethodsKaryotyping analysis, copy number variation sequencing (CNV‐seq), chromosomal microarray analysis (CMA) and WES were parallelly performed for prenatal diagnosis of 19 CCA cases.ResultsThe total detection rate of karyotyping analysis, CMA (or CNV‐seq) and WES were 15.79% (3/19), 21.05% (4/19) and 40.00% (2/5), respectively. Two cases (case 11 and case 15) were diagnosed as aneuploidy (47, XY, + 13 and 47, XX, + 21) by karyotyping analysis and CNV‐seq. Karyotyping analysis revealed an unknown origin fragment (46,XY,add(13)(p11.2)) in case 3, which was further confirmed to originate from p13.3p11.2 of chromosome 17 by CNV‐seq. CMA revealed arr1q43q44 (238923617–246964774) × 1(8.04 Mb) in case 8 with a negative result of chromosome karyotype. WES revealed that 2 of 5 cases with negative results of karyotyping and CNV‐seq or CMA carried pathogenic genes ALDH7A1 and ARID1B.ConclusionParallel genetic tests showed that CNV‐seq and CMA are able to identify additional, clinically significant cytogenetic information of CCA compared to karyotyping; WES significantly improves the detection rate of genetic etiology of CCA. For the patients with a negative results of CNV‐seq or CMA, further WES test is recommended.     

Detection of partial deletion and mosaicism using quantitative fluorescent polymerase chain reaction: Case reports and a review of the literature

BackgroundAneuploidy of chromosomes 13, 18, 21, X, and Y can be detected by the quantitative fluorescence polymerase chain reaction (QF‐PCR) performed with short tandem repeat (STR) markers. Although QF‐PCR is designed to detect whole chromosome trisomy, the partial deletion or mosaic of chromosomes may also be detected.MethodsPartial deletion or mosaic of chromosomes in three cases was detected by QF‐PCR. Karyotyping and chromosome microarray analysis(CMA) were performed. We further reviewed the clinical utility of QF‐PCR in detecting mosaicisms and deletions/duplications.ResultsQF‐PCR demonstrated structurally abnormal 21, X, and Y chromosomes in primary amniotic cells. QF‐PCR results in these three cases showed abnormal peak height/peak area, which could not be interpreted according to the kit instructions. QF‐PCR results suggested that there were partial deletions or mosaicism, which were confirmed by karyotyping and CMA.ConclusionIn addition to detecting trisomies of whole chromosomes, QF‐PCR can also detect deletion and mosaicism of chromosomes 13, 18, 21, X, and Y, which could suggest the presence of copy number variants (CNVs). Additional testing with genetic technologies, such as karyotyping or microarrays, is recommended when an uninformative pattern is suspected.     

羊水原位培养法联合染色体微阵列分析在产前诊断中的应用

摘要:目的评估 羊水原位培养法联合染色体微阵列分析(CMA)技术在产前诊断检出胎儿染色体异常中的应用价值。方法回顾性分析2018年10月至2023年2月于怀化市妇幼保健院因不同产前诊断指征而行羊水穿刺术的3133例孕妇,比较羊.水原位培养法和CMA法在胎儿染色体异常方面的检出率和差异。结果在3133例样本中,双指征组的异常检出率均较单指征组分别增加0.95%(羊水原位培养法)和2.36% ( CMA);两种技术联合检测共检出796例异常(检出率25.41%),其中羊水原位培养法检出300例(9.58%) ,CMA法检出706例(22.53%)。两者均能检出145 例非整倍体异常和31例染色体结构异常,但CMA另增加检出169例提示致病或可能致病的染色体拷贝数变异(CNV)、杂合性缺失(L0H)、杂合性不存在( A0H)/纯合区域(ROH)及单亲体二倍体异常(UPD),而羊水原位培养法增加检出11 例染色体结构异常。两者联合检出嵌合体23例(0.73%)。结论羊水原位培养法与 CMA技术互为补充,联合应用可显著提高胎儿染色体异常的检出率,可为产前遗传咨.询提供更详细准确的信息,有助于孕妇决策是否终止妊娠。