7q部分重复患儿1例的表型及遗传学分析

目的明确1例不明原因生长发育迟缓患儿染色体异常的性质及来源, 分析其与表型的相关性。方法选择2019年7月9日就诊于郑州大学附属儿童医院的1例患儿作为研究对象。用G显带染色体核型分析及单核苷酸多态性微阵列芯片技术(SNP array)对患儿及其父母进行检测。结果 G显带核型分析结合SNP array技术提示患儿染色体核型为:46, XX, dup(7)(q34q36.3), 其父母核型均未见异常。SNP array检测提示患儿染色体7q34q36.3区存在20.6 Mb重复, 具体为arr[hg19]7q34q36.3(138335828₁58923941)×3, 其父母均未查见染色体拷贝数异常。结论患儿为罕见的7q部分重复且为新发变异, 其基因型与表型的相关性有助于临床诊疗及遗传咨询。     

一例22号环状染色体合并22ql3微缺失综合征患儿的临床及遗传学分析

目的探讨1例语言发育滞后患儿的遗传学病因。方法对患儿进行外周血染色体G显带分析以及单核昔酸多态性微阵列芯片(single nucleotide polymorphism microarray,SNP array)检测。结果患儿染色体核型为46,XY,r(22)(pll.2ql3),SNP array检测在22ql3区发现一处1.67 Mb的缺失,具体为arr[Hgl9]22ql3.33(49531302〜51197766)X1O结论患儿同时携带22号环状染色体以及22ql3微缺失,为明确其病因和遗传咨询提供了重要的线索。     

一例8p倒位重复伴末端缺失综合征的表型和遗传学研究

目的:明确1例发育迟缓患儿的染色体拷贝数变异性质和来源,分析其与表型的相关性。方法:应用G显带染色体核型分析以及单核苷酸多态性微阵列芯片(single nucleotide polymorphism array,SNP-array)技术对患儿及其父母进行检测。结果:G显带核型分析结果显示患儿的染色体核型为46,XX,a...     

1例3p部分三体综合征患儿的临床表型与遗传学分析

目的 明确1例体格发育异常合并多发畸形患儿染色体拷贝数变异的性质和来源,并分析基因与表型相关性。方法 采用G显带染色体核型分析及单核甘酸多态性微阵列芯片（SNP-array）技术对患儿进行检测,并用荧光原位杂交（FISH）进行验证。患儿父母外周血样本进行染色体核型分析及其母亲外周血样本进行荧光原位杂交（FISH）分析。结果 G显带染色体核型结果为：46,XY,der(2)t(2;3)(p25.3;p24.1),SNP-array分析结果显示患儿染色体3p26.3p24.1存在30.4Mb重复,2p25.3存在1.39Mb缺失。结论 患儿3p26.3p24.1重复与3p部分三体综合征（partialtrisomy3p syndrome）相关,该重复是导致患儿多发畸形及发育异常的主要遗传学病因。3p部分三体综合征临床表型差异较大,患儿临床特征与基因型有一定关联,临床诊断时应结合临床表型及遗传学检测技术进行综合诊断。     

22q11微缺失综合征胎儿的产前超声特点及遗传学分析

目的:分析胎儿期22q11微缺失综合征(22q11 microdeletion syndrome,22q11DS)病例的产前超声特点和遗传学诊断方法。方法:对2016年11月至2019年11月在福建省妇幼保健院产前诊断中心行产前诊断的4989例胎儿进行单核苷酸多态性微阵列芯片技术(single nucleotide p...     

一例10p15.3缺失及18短臂部分三体患儿的临床表型与遗传学分析

目的明确一例发育迟缓患儿染色体拷贝数变异的性质和来源,分析其与表型的相关性。方法应用单核苷酸多态性微阵列芯片(single nucleotide polymorphism array,SNP array)技术以及G显带染色体核型分析对患儿及其父母进行检测。结果 SNP array分析显示患儿在10p15.3区存在1.2 Mb的微缺失,18p11.21-pter区存在15 Mb的重复,其父母未见染色体拷贝数异常。G显带核型分析结果显示患儿的10号染色体存在结构异常,其父亲染色体核型为46,XY,t(10;18)(p15;p11.2),其母亲核型未见异常。结论患儿10号染色体的结构异常源自其父携带的t(10;18)平衡易位,其核型为46,XX,der(10)t(10;18)(p15;p11.2)pat。10p15.3区微缺失和18p11.21-pter区重复是导致患儿异常表型的原因。     

一例22号环状染色体合并22q13微缺失综合征患儿的临床及遗传学分析

目的 探讨1例语言发育滞后患儿的遗传学病因。方法 对患儿进行外周血染色体G显带分析以及单核苷酸多态性微阵列芯片(single nucleotide polymorphism microarray,SNP array)检测。结果 患儿染色体核型为46,XY,r(22)(p11.2q13),SNP array检测在22q13区发现一处1.67 Mb的缺失,具体为arr[Hg19]22q13.33(49 531 302～51 197 766)×1。结论 患儿同时携带22号环状染色体以及22q13微缺失,为明确其病因和遗传咨询提供了重要的线索。     

三例Kleefstra综合征患儿临床和遗传学分析

目的对3例不明原因的发育迟缓(developmental delay, DD)/智力障碍(intellectual disability, ID)患儿进行临床症状和染色体微阵列分析(chromosome microarray analysis, CMA), 明确其可能的病因。方法采集3例DD/ID患儿的外周静脉血样, 进行CMA检测。结果例1的9号染色体q34.3区段约有190 kb的DNA片段缺失, 包含Kleefstra综合征(OMIM 610253)的关键基因EHMT1(OMIM 607001)的大部分区域;例2和例3为同胞姐妹, CMA检测显示均存在相同的4处染色体片段异常, 其中9号染色体q34.3区域缺失长度分别是154 kb和149 kb, 均包含EHMT1和CACNA1B(OMIM 601012)基因, 其余变异无临床意义。结论 3例患儿的染色体9q34.3微缺失可能是其DD/ID的致病原因, EHMT1是关键基因。     

应用单核苷酸多态性芯片检测7q部分缺失伴发育迟缓患儿一例

目的探讨1例生长发育迟缓患儿的遗传学原因,分析患儿基因组拷贝数变异(copy number variations,CNVs)及其所含基因与临床表型的对应关系。方法用常规G显带技术分析患儿及其父母的外周血染色体核型,用单核苷酸多态微阵列芯片技术(single nucleotide polymorphisms array,SNP-array)进行DNA拷贝数分析。结果患儿及其父母的外周血常规染色体核型分析均未见异常。SNP-array分析结果显示患儿染色体7q11.23区存在1.41 Mb杂合缺失,其缺失与Williams-Beuren综合征相关,父母双方均未见该缺失。结论患儿7号染色体长臂拷贝数变异所致的Williams-Beuren综合征与患儿的发育迟缓及特殊面容等临床表型相关,应用SNP-array技术在临床检测不明原因发育迟缓患儿中具有显著的优势。     

一例罕见的TCF4基因部分缺失型Pitt-Hopkins综合征的遗传学分析

目的探讨1例脑发育落后患儿的遗传学病因。方法采用常规G显带技术分析患儿及其双亲的染色体核型,应用单核苷酸多态性微阵列(single nucleotide polymorphism array,SNP-array)技术对患儿进行全基因组拷贝数变异(copy number variations,CNVs)筛查,并对其双亲进行验证。结果患儿及其双亲染色体G显带核型分析均未见异常。SNP-array检测双亲均未见异常,发现患儿染色体18q21.2区存在172 kb(52957042~53129237)的新发缺失,仅涉及OMIM基因TCF4,导致TCF4第6~8外显子的缺失。结论染色体18q21.2区的缺失与Pitt-Hopkins综合征密切相关。SNP-array检测为该患儿的确诊提供了依据。     

Cytogenetic and molecular genetic analysis of the amniotic fluid cells of a fetus with pseudodicentric isochromosome 22 resulting in partial tetraploidy of 22qCSCD

Objective To diagnose chromosomal abnormalities in amniotic fluid cells by combining karyotyping and single nucleotide polymorphism array (SNP-array) analysis, and to explore the application of SNP-array in routine clinical practice. Methods Conventional G banding was used to karyotype a fetal amniotic fluid sample and the corresponding peripheral blood samples from the parents, followed by SNP- Array analysis of the fetal genomic DNA from the amniotic fluid. Results The karyotype of the amniocytes was 47, XX, +mar. The marker chromosome was further identified as psu idic (22) (q11. 2) by SNP-array analysis, revealing tetraploidy of a 1. 7 Mb fragment in 22q11. 1-qll. 2 interval that involves the critical region for Cat eye syndrome. Conclusion A rare chromosomal abnormality was identified by combining conventional G banding and SNP-array. The high resolution SNP-array could provide more detailed information for determining the origin of chromosomal abnormalities. © 2018 West China University of Medical Sciences. All rights reserved.     

A boy with partial trisomy of chromosome 3q24–q28 from paternal balanced insertion and multiple congenital anomalies

Although many patients with duplication 3q syndrome have been described reports on duplication derivatives from an insertion are rare in the previous literature. Here we describe the genotype and phenotype of a 32‐month‐old boy with a partial trisomy of 3q24–q28. We carefully mapped the aberration with SNP‐array analysis, and found a duplication region of 44 Mb. By conventional cytogenetic techniques including fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY) analysis, the patient was found to have inherited a derivative chromosome 6 from his father, which was contained a direct insertion from 3q24–28. The main clinical features of the patient included severe mental retardation, postnatal developmental delay, ventricular septal defect (VSD), and craniofacial anomalies including cleft palate, frontal bossing, hypertelorism, and a broad nasal bridge. The symptoms partially overlap with previously reported patients with duplication in the same region. Prenatal diagnosis for the fetus of this family was performed based on the results of genetic tests and ultrasonic evaluation. © 2013 Wiley Periodicals, Inc.     

Report of interstitial 22q13.1q13.2 microduplication in two siblings with distinctive dysmorphic features,heart defect and mental retardation

We present two siblings (a boy and a girl) with a submicroscopic 4 Mb duplication at 22q13.1q13.2. Both children manifested infantile hypotonia and delayed motor milestones, congenital heart defect, growth deficiency, and strikingly similar and distinctive craniofacial dysmorphism including brachycephaly, blepharophimosis, short broad-based nose and wide mouth with thin upper lip. The boy had also a submucous cleft palate. Both had fair skin and hair compared with their parents. Both had moderate mental retardation associated with a short attention span. A 4-Mb interstitial duplication at 22q13.1q13.2 was detected by whole genome microarray comparative genomic hybridisation (array CGH) in both children. The duplication was confirmed by fluorescence in situ hybridisation (FISH) analysis. Their parents had normal array CGH results. FISH analysis revealed that the father was a carrier of a balanced interchromosomal submicroscopic insertion of 22q13 into chromosome 11q23, explaining the unbalanced aberration detected in both children. This report narrows down the critical region at 22q13.1q13.2, which is associated with mental retardation, pre- and post-natal growth retardation, hippocampal malformation, psychiatric symptoms such as short attention span and facial dysmorphism including hypertelorism, epicanthal folds and low set/abnormal ears.     

一个染色体14q微缺失的遗传学分析

目的分析1例自闭症、智力低下和癫痫患儿的遗传学病因。方法应用常规G显带染色体核型分析、单核昔酸多态性微阵列(single nucleotide polymorphism array,SNP array)技术检测染色体变异,用高通量测序筛选致病变异位点,Sanger测序验证,查阅数据库及文献分析,以明确缺失区及致病变异基因的病理意义。结果患儿及其父母外周血G显带核型分析结果均未见异常。SNP array检测发现患儿染色体14 qll.2区存在460 kb的缺失,高通量及Sanger测序显示患儿携带NALCN基因新发变异,患儿及其母亲COL4A5基因发生半合子变异。结论染色体14qll.2微缺失与NALCN变异可能与患儿自闭症、智力低下及癫痫等表型相关。     

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...     

易位点在随体的2q37缺失综合征患儿的临床及遗传学分析

目的:对1例儿童多动症患儿进行细胞以及分子遗传学检测以明确诊断。方法:常规进行外周血细胞培养制片及核型分析,荧光原位杂交(fluorescence in situ hybridization,FISH);常规提取外周血DNA,进行单核苷酸多态性微阵列(single nucleotide polymorph...     

一例1q部分三体4q部分单体导致Pierre Robin序列征的遗传学分析

目的:对1例临床诊断为Pierre Robin序列征的患儿进行细胞及分子遗传学分析,寻找遗传学病因。方法:应用外周血染色体核型分析、核苷酸多态性微阵列检测和荧光原位杂交技术,分别对1例表型为下颌小、舌后坠、上呼吸道阻塞、上颚裂开、颈短的患儿及其正常表型的父母进行检测。结果:患儿核型为46,XY,der(4)add(4)...     

Mild “duplication 6q syndrome”: A case with partial trisomy (6)(q23.3q25.3)

We report on a female infant with partial 6q trisomy (46,XX,dir dup(6)(q23.3q25.3)) and phenotypic characteristics of the “duplication 6q syndrome,” including intrauterine growth retardation, dolichocephaly, depressed nasal bridge, almond-shaped palpebral fissures, short neck, flexion-contractures of the wrists, and mild generalized hypertonia. Although clearly belonging to the described “duplication 6q syndrome,” her features were milder than those found in the literature. Comparison of the phenotype of this child with other published reports indicates that specific phenotypic components of the duplication 6q syndrome cannot be attributed to duplication of a specific band or bands on 6q. Am. J. Med. Genet. 68:450–454, 1997. © 1997 Wiley-Liss, Inc.     

Clinical delineation of a patient with trisomy 12q23q24

Trisomies of 12q23q24 have been described rarely in literature. Only a few case-reports have been published so far almost exclusively reporting on neonates or young infants. We present a 16-year-old patient with a trisomy of 12q23.3q24.3. Full phenotypic evaluation at this age comprised: severe growth retardation, developmental delay, intellectual disability and characteristic facial dysmorphisms. Initially, in the proband an insertion was cytogenetically mapped at chromosome 16: der(16)dir ins(16; 12)(q12.1; q24.11q24.31). The mother appeared carrier of a balanced insertion. Subsequent SNP-array analysis in the proband revealed a 16.3 Mb gain of 12q23.3 → 12q24.31. The clinical and molecular findings in this patient are compared with previous literature on cases with overlapping isolated 12q trisomies. The common phenotype observed consists of severe growth retardation, intellectual disability and characteristic facial features with hypertelorism, flat nasal bridge, down-turned mouth and poorly lobulated/low set ears. In addition, pediatric follow up into adolescence showed feeding difficulties requiring gastric tube feeding, recurrent otitis media, progressive contractures of joints and genito-renal problems, speech, communication and behavioral problems. These symptoms should be taken into account in the care and management of children with this condition.