22q11.2微缺失综合征胎儿的产前诊断及家系分析

目的:分析22q11.2微缺失综合征胎儿的产前诊断、亲代验证及妊娠结局,为遗传咨询提供依据。方法:对低深度全基因组测序技术(copy number variation sequencing,CNV-Seq)或染色体微阵列分析(chromosomal microarray analysis,CMA)发现的6例22q11....     

17q12微缺失综合征的产前超声表现和遗传学分析

目的 分析产前孕中晚期17q12微缺失胎儿的超声发现、染色体微阵列分析（CMA）结果、妊娠结局和跟踪随访,探索17q12微缺失综合征的基因组与临床表型的相关性,为产前咨询与诊断提供理论依据。方法 对16例因超声提示胎儿肾脏实质性回声增强或结构异常行侵入性产前诊断羊水或脐带血穿刺,CMA检测结果为17q12微缺失的胎儿进行回顾性研究分析。结果 16例17q12微缺失病例的缺失片段大小在1.42～1.94 Mb,区域内均包含HNF1B、LHX1等相关致病基因。14例为新发突变,2例遗传自母亲。15例肾脏双侧或单侧高回声,1例除肾脏结构畸形外还伴有心脏和肺部结构畸形。5例遗传咨询后选择终止妊娠,11例选择继续妊娠。结论 产前胎儿17q12微缺失综合征的临床表型差异大,超声肾脏回声增强与其存在密切相关性。产前胎儿肾脏高回声行CMA检测,可准确诊断该综合征并明确其基因组学信息,为孕妇妊娠选择提供指导性建议。     

一例18号染色体短臂缺失合并重复胎儿的产前诊断分析

目的:探讨染色体微阵列分析(chromosomal microarray analysis, CMA)技术检测1例无创产前DNA筛查提示18号染色体短臂部分缺失胎儿基因组拷贝数变异的临床价值,为临床遗传咨询提供参考。方法:应用常规染色体G显带技术分析羊水细胞的核型后,CMA技术检测潜在的染色体微缺失或微重复,并对胎儿进...     

22q11.2微缺失综合征产前临床表型的分析

目的探讨产前诊断的22q11.2微缺失综合征病例的不同临床表型,进一步提高对该疾病的认识。方法收集2016年1月至2018年12本院医学遗传中心因产前筛查高风险而就诊,应用染色体微阵列技术确诊的22q11.2微缺失综合征病例,分析其临床表现。结果14651例产前筛查高风险病例中22例(1.5‰)确诊为22q11.2微缺失综合征,其中心脏超声结构异常13例(59.09%),心脏结构异常合并腭裂1例(4.55%),足内翻4例(18.18%),肾脏超声异常3例(13.64%),胎儿发育迟缓并唐氏筛查高风险1例(4.55%);22例22q11.2微缺失综合征中经典型19例(66.36%),非经典型3例(13.64%)。结论本组22q11.2微缺失综合征病例以足内翻为突出临床表现,仅次于心脏结构异常,应予以重视。     

染色体核型分析联合染色体微阵列分析对于产前诊断的价值

目的评估染色体核型分析联合染色体微阵列分析(chromosomal microarray analysis,CMA)对于产前诊断的价值。方法对546例孕妇的羊水同时进行G显带染色体核型分析和CMA检测。结果共检出82例异常,其中43例两种方法的检测结果一致,包括21三体14例、18三体6例、13三体1例、性染色体数目异常14例、染色体缺失4例、染色体重复3例以及嵌合体1例。核型分析漏检15例,包括染色体微缺失9例和染色体微重复6例。CMA漏检16例,包括染色体易位15例,性染色体嵌合1例。有7例核型分析与CMA检测结果不一致。1例核型分析为标记染色体,经CMA检测为9号染色体p13.1p21.1重复。结论染色体核型分析联合CMA技术可以提高染色体异常的检出率,对产前诊断具有重要的意义。     

两例父源性17q12微缺失综合征胎儿的产前诊断和遗传学分析

目的:探讨两例父源性17q12微缺失综合征胎儿的产前诊断和遗传咨询。方法:一名孕妇的两例胎儿的孕中晚期超声检查均提示肾脏异常和羊水过多,应用单核苷酸多态性分析(single nucleotide polymorphism array,SNP-array)分别对第1胎的脐血样本和第2胎的羊水样本进行产前诊断。发现第1胎染...     

产前诊断18号染色体短臂部分缺失胎儿的遗传学分析

目的:分析1例无创产前检测(noninvasive prenatal testing,NIPT)提示18号染色体短臂部分缺失胎儿的遗传学原因。方法:抽取孕妇及丈夫外周血、胎儿羊水进行常规染色体G显带,应用染色体微阵列分析(chromosomal microarray analysis,CMA)对核型结果精确定位,运用着...     

一例2q37微缺失综合征患儿的遗传学分析

目的:对1例2q37微缺失综合征患儿进行诊断和精细定位。方法:对患儿进行染色体G显带、多重连接探针扩增(multiplex ligation-dependent probe amplification,MLPA)、单核苷酸多态性微阵列(single nucleotide polymorphism array,SNP-a...     

TBX1基因与染色体22q11.2微缺失综合征

染色体22q11·2微缺失综合征(22q11·2DS)是人类最常见的染色体微缺失综合征。TBX1基因作为一个T-BOX家族转录因子,其单拷贝缺失可能是22q11·2DS的主要原因之一,它对该综合征临床表征的出现可能有重要作用。TBX1在胚胎生长发育是胚胎咽部分节、咽弓和动脉弓形成、心脏流出道生长与排列及分隔等过程所必需的基因。TBX1受一系列调控基因调节,其本身也调控一系列基因。     

一例先天性唇腭裂胎儿的产前诊断

目的分析1例先天性唇腭裂胎儿的遗传学病因。方法应用染色体微阵列分析技术(chromosomal microarray analysis,CMA)检测胎儿及其家系成员染色体拷贝数变异(copy number variation,CNVs)。结果CMA检测显示胎儿为男性,其染色体Xp11.22区域存在228 kb的DNA片段缺失,染色体9p21.1区域存在721 kb的DNA片段重复,两个CNVs均遗传自亲代。其中染色体Xp11.22区域的CNV为可疑致病性CNV,致病基因为PHF8,9p21.1区域的CNV为良性CNV。结论染色体Xp11.22区域DNA片段缺失可能为胎儿唇腭裂的原因。     

染色体微阵列分析对于胎儿十二指肠梗阻的检测价值

目的:探讨染色体微阵列分析(chromosome microarray analysis,CMA)对于胎儿十二指肠梗阻(duodenal obstruction,DO)的检测价值。方法:选取51例超声提示存在DO的胎儿,将其分为单纯组和合并其他异常组。对其进行CMA检测,并随访所有病例的妊娠结局。结果:在51例胎儿中共...     

两例2p15-p16.1微缺失综合征的产前诊断

目的明确2例畸形流产患儿染色体拷贝数变异,分析引起2p15-p16.1缺失综合征畸形表型的相关基因以及关键区域。方法应用染色体微阵列分析(chromosomal microarray analysis,CMA)技术对畸形流产儿全基因组拷贝数目进行检测,并用计算机软件及生物信息学方法进行分析。结果CMA检测到2例患儿的染色体2p15-16.1区段有约255 kb的DNA拷贝数变异,2例患儿表型符合2p15-p16.1微缺失综合征遗传特征,缺失区域包含XPO1和USP34基因。结论2pl5近端73 kb的片段(chr2:61659957〜61733075,hg19)可能是引起2p15-p16.1微缺失综合征畸形表型的关键区域之一,XPO1和USP34为该缺失综合征的候选基因。     

染色体微阵列分析技术在流产或死胎原因分析中的应用

目的探讨染色体微阵列分析技术(chromosomal microarray analysis,CMA)在流产或死胎原因分析中的应用价值及流产或死胎与染色体异常的关系。方法采用CMA技术对流产绒毛或死胎组织进行全基因组拷贝数变异(copy number variations,CNVs)检测。结果824例流产或死胎样本检测成功率100%,染色体异常381例(46.2%),其中数目异常312例(81.9%),结构异常66例(17.3%),单亲二倍体(uniparental disomy,UPD)3例(0.8%)。数目异常中占比最大的为非整倍体,共287例(92.0%),以16-三体和Turner综合征最为多见,分别为41例(13.1%)和63例(20.2%)。66例染色体结构异常中,26例(39.4%)发生拷贝数重复,20例(30.3%)发生拷贝数缺失,20例(30.3%)发生拷贝数重复伴缺失,其中33例检出临床致病的可能性大。结论CMA是诊断流产或死胎病因的一种可靠、稳定、高分辨的技术。胚胎染色体数目异常是引起临床流产的主要遗传因素,其中以非整倍体变异最为常见。     

染色体微阵列分析技术在高龄孕妇产前诊断中的应用价值

目的:探讨染色体微阵列分析(chromosomal microarray analysis,CMA)对于高龄孕妇异常妊娠的检测价值。方法:回顾分析562例高龄孕妇的CMA检测结果、妊娠结局及新生儿的随访结果。结果:在562份羊水样本中,共检出胎儿染色体异常73例(12.99%),包括21例(3.73%)染色体非整倍体和...     

染色体微阵列分析在超声异常胎儿产前诊断中的应用价值

目的探讨染色体微阵列分析技术(chromosomal microarray analysis,CMA)在超声异常胎儿产前诊断中的应用价值。方法选取B超提示异常的胎儿293例,包括结构异常168例及非结构异常125例。在排除常见的染色体异常核型后,对其羊水行CMA检测。结果CMA共检出致病性拷贝数变异(pathogenic copy number variants,pCNVs)16例,检出率为5.46%。在168例结构异常胎儿中检出pCNVs 10例,检出率为5.95%。在125例非结构异常胎儿中检出pCNVs 6例,检出率为4.80%。结论与传统的染色体核型分析相比,CMA可以提高超声异常胎儿染色体异常的检出率,可作为有效的产前诊断方法。     

Genome-wide gene expression in a patient with 15q13.3 homozygous microdeletion syndrome

We identified a novel homozygous 15q13.3 microdeletion in a young boy, with a complex neurodevelopmental disorder characterized by severe cerebral visual impairment with additional signs of congenital stationary night blindness, congenital hypotonia with areflexia, profound intellectual disability, and refractory epilepsy. The mechanisms by which the genes in the deleted region exert their effect are unclear. In this paper, we probed the role of downstream effects of the deletions as a contributing mechanism to the molecular basis of the observed phenotype. We analyzed gene expression of lymphoblastoid cells derived from peripheral blood of the proband and his relatives to ascertain the relative effects of the homozygous and heterozygous deletions. We identified 267 genes with apparent differential expression between the proband with the homozygous deletion and 3 age- and sex-matched typically developing controls. Several of the differentially expressed genes are known to influence neurodevelopment and muscular function, and thus may contribute to the observed cognitive impairment and hypotonia. We further investigated the role of CHRNA7 by measuring TNFα modulation (a potentially important pathway in regulating synaptic plasticity). We found that the cell line with the homozygous deletion lost the ability to inhibit the activation of tumor necrosis factor-α secretion. Our findings suggest downstream genes that may have been altered by the 15q13.3 homozygous deletion, and thus contributed to the severe developmental encephalopathy of the proband. Furthermore, we show that a potentially important pathway in learning and development is affected by the deletion of CHRNA7.     

Prenatal diagnosis of complex phenotype in a 13-week-old fetus with an interstitial multigene deletion 20q13.13.-q13.2 by chromosomal microarray

We report the first trimester three-dimensional ultrasonographic findings in a 13-week-old fetus with complex phenotype and a de novo 4.7 Mb multigene deletion encompassing chromosome region 20q13.13-q13.2 detected by chromosomal microarray. Fetal sonography detected radial-ray anomalies in the form of bilateral absence of thumbs and the left club hand deformity. The presence of single atrioventricular canal instead of the atrial septal defect typical for Holt-Oram syndrome pointed us to rather suspect the SALL4 related diseases. Central nervous system anomaly in the form of enlarged lateral brain ventricles with choroid plexus shifted backwards was not previously reported as a part of SALL4 related disorders. The pregnancy was terminated at 14 + 3 weeks of pregnancy and the autopsy confirmed ultrasonographic findings. Deleted region included 38 genes, where only SALL4, ADNP and KCNB1 heterozygote pathogenic variants were described to be cause of syndromic forms. Radial ray anomalies are common part of clinical picture of SALL4 related disorders. Despite the lack of prenatally described cases, we hypothesized that maldevelopment of lateral brain ventriculomegaly could be very early sonographic sign of disturbed ADNP expression causing Helsmoortel-Van der Aa syndrome, but in some extent also of KCNB1 related early-onset epileptic encephalopathy. Furthermore, the possible dosage-dependent influence of recessive genes located in this region cannot be also excluded. The use of genome-wide technologies enables the detection of subtle chromosomal imbalances and more precise familial genetic counseling regarding actual and future pregnancies.