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1.
研究目的:通过对一个中国Nance-Horan综合征家系的临床表型及基因突变分析,揭示本家系的致病遗传机制。研究方法:对该Nance-Horan综合征家系的一个男性患者进行全外显子组测序,结合此家系临床表型及遗传方式分析,选定X染色体上NHS基因上的一个无义突变c.322GT(E108X)为可疑致病突变。通过聚合酶链式反应(PCR)和Sanger测序,对该家系内其他成员进行NHS基因突变分析,同时对50名健康对照者的NHS基因的突变检测结果进行对比。另外,将该突变的位点第108位氨基酸残基进行多物种NHS蛋白内序列比对。最后,对该家系成员眼部及全身的临床特点进行全面检查和分析。重要结论:全外显子组测序结合Sanger测序发现NHS基因第一个外显子上的c.322GT(E108X)突变为引起该家系临床病变的突变位点;多物种NHS蛋白内序列比对发现该突变位点第108位氨基酸残基位于高度保守区;临床表型分析发现该家系内存在表型异质性。此家系为国内首次报道的无义突变引起的Nance-Horan综合征家系。  相似文献   

2.
目的:寻找一个Lynch综合征患者所在家系携带的DNA错配修复基因突变,探讨各突变对肿瘤发生发展的影响。创新点:MLH1的第19号外显子c.2250_2251insAA移码突变既往被认为是意义未名突变,而我们的研究为明确该突变的致病意义提供了依据。另外,我们首次报道了MLH3基因第1号外显子c.1397C>A突变。该突变有可能使Lynch综合征患者的发病年龄提前。方法:运用免疫组织化学技术检测家系先证者肿瘤组织中错配修复基因蛋白的缺失情况,使用二代测序技术通过先证者血标本明确患者所携带的突变。同时运用Sanger法检测家系其他成员该突变的携带情况以明确突变对肿瘤发生发展的影响。结论:我们在患者体内发现MLH1基因第19号外显子移码突变(c.2250_2251insAA)以及MLH3基因第1号外显子c.1397C>A突变。在患者家系中,我们仅检测到有MLH1突变,因此该突变极有可能为致病突变。  相似文献   

3.
目的:临床表型-基因型关联分析筛查Leber先天性黑矇(LCA)家系候选基因,确定其分子遗传病因。创新点:成功应用临床表型-基因型关联分析鉴定LCA家系致病基因,并发现新的RDH12基因复合杂合突变。方法:收集一个中国常染色体隐性遗传三代LCA家系,详细分析该家系眼部表型特征(图1和表1),经临床表型-基因型关联分析确定RDH12为候选基因。Sanger测序发现新的RDH12基因复合杂合突变(图2),目标序列捕获高通量测序技术排除其他已知LCA相关基因(表2)。该家系成员基因型显示完整的共分离(图3),同时在600例普通人群中未发现该突变。结论:RDH12基因复合杂合突变可能为该LCA家系的致病基因,临床表型-基因型关联分析在LCA分子遗传学诊断中有重要价值。  相似文献   

4.
研究目的:寻求该房间隔缺损家系遗传致病原因。创新要点:1.鉴定出一个全新的家族性房间隔缺损相关性TBX20突变;2.首次使用全外显子测序结合先天性心脏病相关基因过滤的方法来研究小家系遗传致病因素;3.TBX20的T-box DNA结合域的突变与先天性心脏病有关。研究方法:对一个临床发现的房间隔缺损家系(图1a)的先证者进行全外显子测序,运用公共数据库过滤后,使用先天性心脏病相关基因再次过滤,得到了19个候选基因;然后,运用SIFT、Polyphen-2和MutationTaster等软件预测,排除了13个多态性位点(表2);最后,运用共分离检测(聚合酶链式反应产物直接测序),找到该家系致病的遗传因素,即TBX20基因发生了错义突变(D176N)(图2),该突变位点在ESP和dbSNP数据库中也未曾发现,且该位点在多种生物中高度保守(图1c)。重要结论:1.本研究发现的TBX20突变(D176N)是该房间隔缺损家系致病的原因,同时该突变位点为世界上首次报道;2.全外显子测序结合先天性心脏病相关基因过滤是一个分析小家系遗传致病因素的有效又经济的方法。  相似文献   

5.
研究目的:对1个Axenfeld-Rieger综合征家系的临床特点及基因突变进行研究,探索Axenfeld-Rieger综合征发病的遗传机制。研究方法:对该Axenfeld-Rieger综合征家系进行全面临床检查,对家系成员应用聚合酶链反应(PCR)扩增PITX2基因和FOXC1基因的所有外显子及相邻内含子,对其产物进行直接测序并对PITX2基因第5个外显子进行克隆测序。选取100名健康者作为对照组,应用PCR扩增PITX2基因第5个外显子并进行直接测序。应用SWISS-MODEL软件对野生型和突变型的PITX2蛋白同源域进行建模分析。重要结论:该Axenfeld-Rieger综合征家系的眼部表型多样,但是各患者的全身系统异常却呈现一致性(见图2;表1)。基因测序结果显示先证者及其他患者均具有PITX2基因杂合突变c.198_201delins TTTCT(p.M66Ifs*133)。尽管PITX2基因突变引起Axenfeld-Rieger综合征已经被广泛证实,但是PITX2基因缺失/插入移码突变引起的Axenfeld-Rieger综合征仅被报道过一次,我们的研究首次在中国人群中揭示了这种罕见的突变方式。  相似文献   

6.
目的:探究MARVELD2在中国非综合征耳聋(NSHL)人群中的突变频谱和突变频率。创新点:发现MARVELD2突变频谱具有明显种族特异性。中国NSHL人群中的突变位点及频率不同于已报道的其他人群,并首次筛选到新致聋候选突变MARVELD2 c.730GA。本研究有助于进一步阐释MARVELD2在NSHL中的作用。方法:收集283例NSHL患者外周血,提取基因组DNA,涉及9对引物覆盖MARVELD2基因编码区,经聚合酶链反应(PCR)扩增后Sanger测序。测序结果与参考序列比对,获得的MARVELD2变异位点通过正常人群频率比较、氨基酸保守性分析、氨基酸性质分析、SIFT和PolyPhen有害性预测及蛋白结构功能预测分析等进一步筛选得到耳聋候选突变位点。结论:中国NSHL人群的MARVELD2突变位点与巴基斯坦人群,以及斯洛伐克、匈牙利和捷克罗马人群不同,具有明显的种族特异性。本研究在283个NSHL病例中共鉴定了11个变异位点。其中,c.730GA突变可能影响MARVELD2蛋白的正常功能,与NSHL致病有较高的相关性,是一个候选致聋突变。  相似文献   

7.
通过PCR扩增并克隆测序,获得了鳡（Elopichthys bambusa）线粒体ND5基因序列,该基因全长为1836bp,编码611个氨基酸残基的蛋白质,其起始密码子为ATG,终止密码子为TAA.分析该基因碱基组成及密码子使用情况,发现A＋T含量高于G＋C,并且在密码子第三位点存在明显的反G偏倚.将鳡ND5基因序列与GenBank中其他10个物种的ND5基因序列进行比对,结果表明鳡与鲢鱼的亲缘关系最近,青鱼次之.用NJ法构建11个物种的系统进化树,结果表明雅罗鱼亚科、鲌亚科和鲢亚科之间的亲缘关系很近,而鲤亚科与它们之间的亲缘关系相对较远.  相似文献   

8.
应用RT-PCR的方法从拟南芥cDNA中克隆了AFH14的全序列,并对其功能结构域进行分析。发现所克隆的目的基因编码区全长3 102 bp,与基因组序列比对发现该基因包含18个内含子和18个外显子,编码1 033个氨基酸残基。通过与其它formin成员的序列比对分析,发现AFH14是一个典型的拟南芥II型formin,包括PTEN结构域。  相似文献   

9.
分析莆田地区非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因突变的情况。收集138例莆田地区非小细胞肺癌组织,采用EliVisionTM plus免疫组织化学染色检测癌组织中EGFR基因外显子18、19、20及2l的突变,同时分析其突变与临床特征的关系。结果:138例NSCLC中共检出52例EGFR基因突变,EGFR突变阳性率为37.7%;外显子19和21突变占总突变的92.3%;腺癌突变发生率占突变总数的73.1%;女性EGFR基因突变率(55.0%)显著高于男性(30.6%)(P<0.05)。结果表明:莆田地区NSCLC患者EGFR基因突变以外显子19和21突变为主,女性患者和腺癌患者是选用EGFR酪氨酸激酶抑制剂的优势人群。  相似文献   

10.
研究目的:I型Crigler-Najjar综合征(CN-I)为先天性间接胆红素血症的最严重的一种,是由位于染色体2q37的葡萄糖醛酸转移酶基因(UGT1A1)的纯合或复合杂合突变引起的一种罕见的遗传性疾病。本研究对来自两个无关家庭的两例临床诊断为CN-I的患儿及父母进行UGT1A1基因分子遗传学分析。研究方法:经知情同意后,采集两例患儿及父母外周血;聚合酶链式反应(PCR)扩增UGT1A1基因5个外显子及外显子-内含子交界处,进行测序分析。应用实时定量PCR(qRT-PCR)测定其中一例患者UGT1A1基因的拷贝数。重要结论:本研究在两例CN-I型患儿中检测到3个UGT1A1基因突变:c.239_245delCTGTGCC(p.Pro80HisfsX6)、c.1253delT(p.Met418ArgfsX5)和c.1156GT(p.Val386Phe)。前两个突变均为新发的移码突变,预测提前出现终止密码或诱发RNA降解;而突变c.1156GT(p.Val386Phe)的致病机制尚需进一步研究。  相似文献   

11.

Objective

To screen mutations in FERM domain-containing protein 7 (FRMD7) gene in two Chinese families with X-linked idiopathic congenital nystagmus (XLICN).

Methods

Common ophthalmic data and peripheral blood of two Chinese XLICN families (families A and B) were collected after informed consent. Genomic DNA was prepared from the peripheral blood of members of the two families and from 100 normal controls. Mutations in the FRMD7 gene were determined by directly sequencing polymerase chain reaction (PCR) products.

Results

We identified a novel mutation c.980_983delATTA compound with c.986C>A mutation in the 11th exon of FRMD7 in family B, and a previously reported splicing mutation c.782G>C (p.R261G) in family A. The mutations were detected in patients and female carriers, while they were absent in other relatives or in the 100 normal controls.

Conclusions

Our results expand the spectrum of FRMD7 mutations in association with XLICN, and further confirm that the mutations of FRMD7 are the underlying molecular mechanism for XLICN.  相似文献   

12.

Background

Leber congenital amaurosis (LCA) is a group of clinically and genetically heterogeneous retinal dystrophy. To date, 22 genes are known to be responsible for LCA, and some specific phenotypic features could provide significant prognostic information for a potential genetic etiology. This study is to identify gene variants responsible for LCA in a Chinese family using direct Sanger sequencing, with the help of phenotype-genotype correlations.

Methods

A Chinese family with six members including two individuals affected with LCA was studied. All patients underwent a complete ophthalmic examination. Based on phenotype-genotype correlation, direct Sanger sequencing was performed to identify the candidate gene on all family members and normal controls. Targeted next-generation sequencing was used to exclude other known LCA genes.

Results

By Sanger sequencing, we identified two novel missense variants in the retinol dehydrogenase 12 (RDH12) gene: a c.164C>A transversion predicting a p.T55K substitution, and a c.535C>G transversion predicting a p.H179D substitution. The two affected subjects carried both RDH12 variants, while their parents and offspring carried only one of heterozygous variants, showing complete cosegregation of the variants. The compound heterozygous variants were not present in 600 normal controls. Besides, the RDH12 variants were confirmed by targeted next-generation sequencing.

Conclusions

The RDH12 compound heterozygous variants might be the cause of the LCA family. Our study adds to the molecular spectrum of RDH12-related retinopathy and offers an effective example of the power of phenotype-genotype correlations in molecular diagnosis of LCA.
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13.
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14.

Objective

Heavy ion beam, which has emerged as a new mutagen in the mutation breeding of crops and ornamental plants, is expected to result in the induction of novel mutations. This study investigates the morphological and biochemical responses of Oryza sativa toward different doses of carbon ion beam irradiation.

Methods

In this study, the dry seeds of O. sativa were irradiated at 0, 20, 40, 60, 80, 100, and 120 Gy, followed by in-vitro germination under controlled conditions. Morphological and biochemical studies were conducted to investigate the morphological and physiological responses of O. sativa towards ion beam irradiation.

Results

The study demonstrated that low doses (10 Gy) of ion beam have a stimulating effect on the height, root length, and fresh weight of the plantlets but not on the number of leaves. Meanwhile, doses higher than 10 Gy caused reductions in all the morphological parameters studied as compared to the control samples. The highest total soluble protein content [(2.11±0.47) mg/g FW] was observed in plantlets irradiated at 20 Gy. All irradiated plantlets were found to have 0.85% to 58.32% higher specific activity of peroxidase as compared to the control samples. The present study also revealed that low doses of ion beam (10 and 20 Gy) had negligible effect on the total chlorophyll content of O. sativa plantlets while 40 Gy had a stimulating effect on the chlorophyll content. Plantlets irradiated between 40 to 120 Gy were shown to be 0.38% to 9.98% higher in total soluble nitrogen content which, however, was not significantly different from the control samples.

Conclusions

Carbon ion beam irradiation administered at low to moderate doses of 10 to 40 Gy may induce O. sativa mutants with superior characteristics.  相似文献   

15.
研究目的:探索不同肝功能指数对镇静药咪达唑仑的敏感性以及脑电双频谱指数(BIS)的预测意识消失的影响。创新要点:明确不同肝功能状态的患者对中枢抑制药的敏感性以及BIS预测意识消失概率发生的敏感性。指导临床医生根据患者的肝功能状态合理使用中枢抑制药以及正确利用BIS预测镇定深度。研究方法:选择意识消失作为研究终点,以50%患者意识消失时的咪唑安定的浓度以及BIS值作为观察指标。重要结论:终末期肝病患者对中枢镇静药咪唑安定更敏感,该类患者在BIS预测意识消失概率发生的敏感性存在差异。  相似文献   

16.
Objective:The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase(MTHFR) C677T excision repair cross-complementation group 1(ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer(NSCLC).Methods:A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens.The polymorphisms of MTHFR C677T,ERCC1 C8092A,and ERCC1 C118T were genotyped using the TaqMan methods.Results:The overall response rate was 28.9%.Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype(TT or CT)(41.2% versus 19.1%,P=0.01).Median time to progression(TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype(7.6 months versus 5.0 months,P=0.003).No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival.Conclusions:Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.  相似文献   

17.
Objective:To evaluate the pharmacological effects of traditional Chinese medicine,bear bile capsule and Huangqi granule,on recurrent parotitis in children.Methods:In this prospective,controlled,and randomized study,a total of 151 young children were divided into three groups:Group A included massaging the children’s parotid region and melting vitamin C in their mouth daily;Group B included swallowing bear bile capsule and Huangqi granule daily;and Group C included massages and vitamin C as prescribed in Group A,and traditional Chinese medicine as prescribed in Group B.Children were treated individually for one month and then a follow-up study was conducted for 1 to 3.5 years.Analysis of variance(ANOVA) and Ridit analysis were employed for statistical analysis.Results:The recurrence rate decreased in every group,but was significantly more in Groups B and C when compared to Group A.The recurrences significantly decreased(P<0.01) in Group B and their recovery rate was as high as 63%,significantly better than those of the other groups(P<0.01).Conclusions:Huangqi and bear bile could be a novel clinical approach for treating recurrent parotitis in children.  相似文献   

18.

Objective

A study in a Caucasian population has identified two single-nucleotide polymorphisms (SNPs) in ZNF533, one in DOCK4, and two in IMMP2L, which were all significantly associated with autism. They are located in AUTS1 and AUTS5, which have been identified as autism susceptibility loci in several genome-wide screens. The present study aimed to investigate whether ZNF533, DOCK4, and IMMP2L genes are also associated with autism in a northeastern Chinese Han population.

Methods

We performed a similar association study using families with three individuals (one autistic child and two unaffected parents). A family-based transmission disequilibrium test (TDT) was used to analyze the results.

Results

There were significant associations between autism and the two SNPs of ZNF533 gene (rs11885327: χ 2=4.5200, P=0.0335; rs1964081: χ 2=4.2610, P=0.0390) and the SNP of DOCK4 gene (rs2217262: χ 2=5.3430, P=0.0208).

Conclusions

Our data suggest that ZNF533 and DOCK4 genes are linked to a predisposition to autism in the northeastern Chinese Han population.  相似文献   

19.
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20.
Erythropoietic protoporphyria (EPP), an autosomal dominant disease, is caused by partial deficiency of ferrochelatase (FECH), which catalyzes the terminal step of heme biosynthesis because of loss-of-function mutations in the FECH gene. To date, only a few cases have been described in Asia. In this study, we describe the clinical features of two Chinese patients with EPP, with diagnosis confirmed by the increase of free protoporphyrin in erythrocytes, detection of plasma fluorescence peak at 630–634 nm, and analysis of FECH gene mutations. Using gene scanning, we identified a small deletion in the FECH gene (c.973 delA) in one proband (patient A) and a pathogenic FECH mutation (c.1232 G>T) in the other (patient B) and also observed some nucleotide variations (c.798 C>G, c.921 A>G, IVS1?23 C>T, IVS3+23 A>G, IVS9+35 C>T, and IVS3?48 T>C) in these patients. The family pedigree of patient A was then established by characterization of the genotype of the patient’s relatives. We also analyzed the potential perniciousness of the missense mutation with bioinformatic software, Polyphen and Sift. In summary, Chinese EPP patients have similar manifestations to those of Caucasians, and identification of the Chinese FECH gene mutations expands the FECH genotypic spectrum and may contribute to genetic counseling.  相似文献   

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