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Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature 被引量:1
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作者 Xiao-Hui Guo Xin Jin +1 位作者 Bin Wang Zhao-Yan Wang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第1期47-52,共6页
AIM:To detect the pathogenic gene variant in a family with neurofibromatosis type 1(NF1).METHODS:This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology.After detect... AIM:To detect the pathogenic gene variant in a family with neurofibromatosis type 1(NF1).METHODS:This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology.After detecting the suspicious pathogenic variant type,the pathogenic variant sites of the patient and the patient’s family members were verified by multiple ligation dependent probe amplification and Sanger sequencing.Sift,polyphen-2,Mutation Taster and GERP++software were used to predict the pathogenicity of the unknown loci.The clinical data,diagnosis and treatment process of the patients were reviewed.Using the keyword“NF1;frameshift pathogenic variant”,relevant literature was gathered for analysis from Chinese and international databases,with articles dating from the establishment of each database to April 2022.RESULTS:A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient.The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497.Sanger sequencing validation and segregation analysis were performed,which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family.This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA(p.I1497Nfs*12).Relevant literature retrieval found 7 Chinese articles and 12 foreign articles.With NF1 gene mutation,mutation types are diverse,including point mutation,frameshift mutation,splice site mutation,exon mutation,chimeric mutation and de novo mutation.Foreign reports are based on autosomal dominant inheritance.CONCLUSION:This study’s results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family,expanding the mutational spectrum of the NF1 gene. 展开更多
关键词 neurofibromatosis type 1 frameshift pathogenic variant monozygotic twins
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A novel frameshift mutation in the beta-subunit of the epithelial sodium channel gene caused Liddle syndrome
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作者 Peng Fan Chaoxia Lu +7 位作者 Di Zhang Kunqi Yang Peipei Lu Ying Zhang Xu Meng Yaxin Liu Xue Zhang Xianliang Zhou 《中国循环杂志》 CSCD 北大核心 2018年第S01期162-162,共1页
Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmat... Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing. 展开更多
关键词 frameshift MUTATION the EPITHELIAL sodium channel GENE Liddle SYNDROME
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Severe Wolfram Syndrome Caused by a Novel Frameshift Mutation in <i>WFS1</i>Gene: Effect on the WFS1/CaM Interaction and Phenotype-Genotype Correlation
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作者 Mouna Tabebi Rahma Felhi +6 位作者 Houcem Elomma Mrabet Wajdi Safi Baha Zantour Mohamed Habib Sfar Mohammed Abid Mouna Mnif Feki Faiza Fakhfakh 《Open Journal of Genetics》 2021年第4期77-92,共16页
Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined <span style="font-family:Verdana;">by early onset of diabetes mellitus and progr... Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined <span style="font-family:Verdana;">by early onset of diabetes mellitus and progressive optic and hearing impairment. Only few data are available concerning the association between clinical and molecular aspects of the WFS. We present a consanguineous family with a patient presenting an early onset of WFS and severe manifestations. Sequencing of </span><i><span style="font-family:Verdana;">WFS1</span></i><span style="font-family:Verdana;"> gene was performed for all the family members to search for responsible mutation and bioinformatics tools </span><span style="font-family:Verdana;">were </span><span style="font-family:;" "=""><span style="font-family:Verdana;">conducted to predict its effect on structure and function of the protein. We have detected a novel frameshift mutation in the proband at homozygous state and at the heterozygous state in the parents who have no WFS manifestations. In silico analysis predicted the pathogenicity of the mutation and could lead to a complete loss of its function. Thus, 3D modeling showed that the mutation abolishes the interaction of the CaM binding region to the N-terminal of WFS1 and then impairs the W</span><span style="font-family:Verdana;">FS1-CaM complex formation. Genotype-phenotype correlation study show</span><span style="font-family:Verdana;">s that the novel mutation predisposes to early onset of diabetes and severe symptoms observed in the proband. We also report the effect of the frameshift mutation on the CaM-WFS1 impaired binding, and we discuss its possible consequence in pancreatic </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-cells dysfunction and its role in the early onset of diabetes. In conclusion, the combination of impaired functions of WFS1 including unproper interaction of the CaM, Ca</span><sup><span style="font-family:Verdana;">2+</span></sup><span style="font-family:Verdana;"> uptake, mitochondrial dysfunction, and apoptosis under the ER stress could be involved in the severe phenotype and early onset of WFS of our patient.</span></span> 展开更多
关键词 Wolfram Syndrome WFS1 frameshift Mutation WFS1-CaM Binding
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Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed–1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element
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作者 Hongying Li Jianrui Li +15 位作者 Jiayu Li Hu Li Xuekai Wang Jing Jiang Lei Lei Han Sun Mei Tang Biao Dong Weiqing He Shuyi Si Bin Hong Yinghong Li Danqing Song Zonggen Peng Yongsheng Che Jian-Dong Jiang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2024年第6期2567-2580,共14页
The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the... The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials,decreases the efficiency of programmed–1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion.Carrimycin binds directly to the coronaviral frameshift-stimulatory element(FSE)RNA pseudoknot,interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes.Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses.Because the FSE mechanism is essential in all coronaviruses,carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA.This finding may open a new direction in antiviral drug discovery for coronavirus variants. 展开更多
关键词 Carrimycin CORONAVIRUS Broad-spectrum antiviral activity Programmed-1 ribosomal frameshifting RNA pseudoknot Antiviral agent RNA target Synergistic inhibitory effect
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假尿苷修饰体外转录mRNA在翻译过程中发生的+1核糖体框架移码
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作者 于永利 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2024年第3期269-273,共5页
为应对世界范围内的COVID-19疫情,假尿苷(Ψ)修饰的体外转录mRNA(Ψ-IVT-mRNA)被授权应用于SARS-Cov-2 mRNA疫苗。最近,Ψ-IVT-mRNA被发现在翻译蛋白质时发生核糖体“滞顿”,导致+1核糖体移码,在体外和体内翻译出异常的蛋白质。在接种SA... 为应对世界范围内的COVID-19疫情,假尿苷(Ψ)修饰的体外转录mRNA(Ψ-IVT-mRNA)被授权应用于SARS-Cov-2 mRNA疫苗。最近,Ψ-IVT-mRNA被发现在翻译蛋白质时发生核糖体“滞顿”,导致+1核糖体移码,在体外和体内翻译出异常的蛋白质。在接种SARS-Cov-2 mRNA疫苗的人群,这种异常蛋白可能激发脱靶T细胞反应或抗体反应或产生其它意想不到的副作用。这一发现对研制有效“安全”的mRNA疫苗/药物有“警示”和指导意义。 展开更多
关键词 SARS-CoV-2疫苗 体外转录mRNA 假尿苷修饰 核糖体框架移码
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常染色体隐性遗传性痉挛性共济失调一例并文献复习
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作者 刘升阳 闫雨萌 +3 位作者 安利 孙辰婧 刘建国 姚生 《北京医学》 CAS 2024年第5期385-389,共5页
目的探讨常染色体隐性遗传性痉挛性共济失调(autosomal recessive spastic ataxia of Charlevoix Saguenay,ARSACS)患者的临床、影像、病理及遗传学特点。方法选取2019年12月23日解放军总医院第六医学中心神经内科患者1例,回顾分析患者... 目的探讨常染色体隐性遗传性痉挛性共济失调(autosomal recessive spastic ataxia of Charlevoix Saguenay,ARSACS)患者的临床、影像、病理及遗传学特点。方法选取2019年12月23日解放军总医院第六医学中心神经内科患者1例,回顾分析患者的临床、影像、腓肠神经活检病理及基因突变特点,并复习既往文献。结果本例患者男,21岁,2岁起病,首次发作表现为双下肢力弱及不耐受疲劳,11岁出现共济失调步态,17岁出现剪刀步态。主要临床表现为典型小脑共济失调、痉挛性截瘫和周围神经病“三联征”,头颅MRI示脑桥基底部和被盖部T2WI轴位横向条带状短T2信号,呈“4行2列”排列;脑桥小脑脚增粗,小脑上蚓部萎缩。神经电生理示运动神经潜伏期延长及波幅减低、传导速度减慢,感觉神经传导未检出确切波形。双侧胫骨前肌呈神经源性损害。腓肠神经活检病理示神经束内大、小有髓神经纤维密度中度减少,及散在分布的轴索变性及薄髓纤维。患者ARSACS基因存在p.D968Vfs*13和p.D1903Yfs*31的2处移码突变,分别来自患者父亲和母亲。既往文献未发现该突变报道,考虑为新发突变。结论ARSACS患者临床表现为典型“三联征”,头颅影像学表现为脑桥轴位T2WI呈“4行2列”排列的横向条带状短T2信号,腓肠神经活检呈慢性活动性轴索变性及髓鞘脱失,ARSACS基因新发突变。 展开更多
关键词 常染色体隐性遗传性痉挛性共济失调 三联征 轴索变性 神经活检 移码突变
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KMT2D基因新发变异致歌舞伎面谱综合征一例
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作者 张丹莉 石雪冬 +4 位作者 李建磊 周立飞 王文艺 张萍萍 李亚丽 《国际生殖健康/计划生育杂志》 CAS 2024年第6期471-474,共4页
歌舞伎面谱综合征(Kabuki syndrome,KS)是一种罕见的多系统发育异常的疾病,常在儿童期发病。报告1例因智力低下、发育迟缓就诊的患儿,经全外显子组测序检测相关致病基因,并对家庭成员进行Sanger DNA测序验证,发现患儿KMT2D基因存在c.675... 歌舞伎面谱综合征(Kabuki syndrome,KS)是一种罕见的多系统发育异常的疾病,常在儿童期发病。报告1例因智力低下、发育迟缓就诊的患儿,经全外显子组测序检测相关致病基因,并对家庭成员进行Sanger DNA测序验证,发现患儿KMT2D基因存在c.6752delC(p.S2251Cfs*13)移码突变,经ClinVar和人类基因突变数据库(Human Gene Mutation Database,HGMD)等数据库搜索未发现此突变位点的记载,其父母未携带该变异,此突变为新发的致病性突变。基因检测结果提示患儿为KMT2D基因新发变异所致的KS1型,该突变位点丰富了KS的临床基因突变谱及临床数据,对于该病家系的遗传咨询具有重要意义。 展开更多
关键词 歌舞伎面谱综合征 KMT2D基因 移码突变 治疗 病例报告
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Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome 被引量:5
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作者 Hou-fa YIN Xiao-yun FANG +5 位作者 Chong-fei JIN Jin-fu YIN Jin-yu LI Su-juan ZHAO Qi MIAO Feng-wei SONG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2014年第1期43-50,共8页
Objective: Axenfeld-Rieger syndrome (ARS) is phenotypically and genetically heterogeneous. In this study we identified the underlying genetic defect in a Chinese family with ARS. Methods: A detailed family history... Objective: Axenfeld-Rieger syndrome (ARS) is phenotypically and genetically heterogeneous. In this study we identified the underlying genetic defect in a Chinese family with ARS. Methods: A detailed family history and clinical data were recorded. The ocular phenotype was documented using slit-lamp photography and systemic anomalies were also documented where available. The genomic DNA was extracted from peripheral blood leukocytes. All coding exons and intron-exon junctions of paired-like homeodomain transcription factor 2 (PITX2) gene and the forkhead box C1 (FOXC1) gene were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Variations detected in exon 5 of PITX2 were further evaluated with cloning sequencing. The exon 5 of PITX2 was also sequenced in 100 healthy controls, unrelated to the family, for comparison. Structural models of the wild type and mutant homeodomain of PITX2 were investigated by SWISS-MODEL. Results: Affected individuals exhibited variable ocular phenotypes, whereas the systemic anomalies were similar. After direct sequencing and cloning sequencing, a heterozygous deletion/insertion mutation c. 198_201delinsTTTCT (p.M661fs*133) was revealed in exon 5 of PITX2. This mutation co-segregated with all affected individuals in the family and was not found either in unaffected family members or in 100 unrelated controls. Conclusions: We detected a novel frameshift mutation p.M661fs*133 in PITX2 in a Chinese family with ARS. Although PITX2 mutations and polymorphisms have been re- ported from various ethnic groups, we report for the first time the identification of a novel deletion/insertion mutation that causes frameshift mutation in the homeodomain of PITX2 protein. 展开更多
关键词 Axenfeld-Rieger syndrome PITX2 gene FOXC1 gene frameshift mutation HOMEODOMAIN
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Novel Mutation of Cleidocranial Dysplasia-related Frameshift Runt-related Transcription Factor 2 in a Sporadic Chinese Case 被引量:2
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作者 Xue-Yan Qin Pei-Zeng Jia +3 位作者 Hua-Xiang Zhao Wei-Ran Li Feng Chen Jiu-Xiang Lin 《Chinese Medical Journal》 SCIE CAS CSCD 2017年第2期165-170,共6页
Background: Cleidocranial dysplasia (CCD) is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of ... Background: Cleidocranial dysplasia (CCD) is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 (RUNX2). Here, we report a sporadic Chinese case presenting typical symptoms of CCD. Methods: We made genetic testing on this sporadic Chinese case and identified a novel RUNX2 ffameshift mutation: c.1111 dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2. Results: RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated. Conclusions: We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes. 展开更多
关键词 Cleidocranial Dysplasia frameshift Mutation Runt-related Transcription Factor 2
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PAX6新发移码和无义变异导致中国先天性无虹膜病一家系临床表型和基因型分析
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作者 王冬冬 杜娇 +3 位作者 黄子旭 但汉东 林作鹏 宋宗明 《中华实验眼科杂志》 CAS CSCD 北大核心 2024年第10期927-931,共5页
目的分析先天性无虹膜病一家系的临床表现及其致病原因,并分析候选变异对蛋白结构的影响。方法采用家系调查研究方法,收集2023年6月于河南省立眼科医院就诊的中国河南地区汉族先天性无虹膜病一家系2代3人的临床资料,其中患者1例。详细... 目的分析先天性无虹膜病一家系的临床表现及其致病原因,并分析候选变异对蛋白结构的影响。方法采用家系调查研究方法,收集2023年6月于河南省立眼科医院就诊的中国河南地区汉族先天性无虹膜病一家系2代3人的临床资料,其中患者1例。详细询问患者及其家系成员病史,并进行全面眼科检查,包括视力、眼压、眼前节照相、彩色眼底照相、超声生物显微镜、光学相干断层扫描等。采集该家系成员外周血,对患者进行全外显子组测序,其他成员采用Sanger测序验证。对新发现的变异位点进行致病性和蛋白结构分析。结果先证者男,23岁,双眼视力较差、无虹膜、角膜变性、晶状体轻度混浊、前房较浅且眼压高、周边视网膜变性、黄斑发育不良。先证者父母临床表型未见明显异常。全外显子组测序显示,PAX 6基因外显子10存在移码和无义变异c.734_735del(p.Arg245Asnfs*20),该变异为第734~735位碱基缺失,导致其245位精氨酸变异为天冬酰胺,并在其后19个氨基酸处提前出现终止密码子。该变异在HGMD、Clinvar、千人基因组和gnomAD数据库均未见收录。先证者父母未携带该变异,符合家系共分离。通过SMART工具进行亚结构鉴定发现该变异位于HOX结构域中。氨基酸保守性分析发现PAX 6基因翻译的氨基酸序列第245位精氨酸在人、小家鼠、家犬、非洲爪蟾、猕猴等物种中高度保守。经ACMG《序列变异解读标准和指南》评估,该变异被分类为致病性变异(PVS1+PS2+PM2+PP3)。蛋白结构分析显示,PAX6蛋白的同源结构域和富含脯氨酸-丝氨酸-苏氨酸的结构域缺失。结论PAX 6基因新发移码和无义致病性变异c.734_735del(p.Arg245Asnfs*20)是该先天性无虹膜病家系的致病变异位点,该变异使PAX6蛋白同源结构域和富含脯氨酸-丝氨酸-苏氨酸的结构域缺失。 展开更多
关键词 无虹膜 家系 移码变异 PAX6基因 基因分析
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IRF8新发移码突变的基因功能分析
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作者 李乐盈 陈尧 +3 位作者 周维涛 何晨 张端午 钱莉玲 《复旦学报(医学版)》 CAS CSCD 北大核心 2024年第3期359-367,共9页
目的对反复肺炎患儿队列病因筛查中发现的干扰素调节因子8基因(interferon regulator factor 8,IRF8)新发突变(c.1266dupA)进行分子细胞水平的功能研究与验证。方法针对IRF8突变序列构建野生与突变蛋白过表达载体,通过质粒转染或构建慢... 目的对反复肺炎患儿队列病因筛查中发现的干扰素调节因子8基因(interferon regulator factor 8,IRF8)新发突变(c.1266dupA)进行分子细胞水平的功能研究与验证。方法针对IRF8突变序列构建野生与突变蛋白过表达载体,通过质粒转染或构建慢病毒感染不同工具细胞,通过qPCR、Western blot、免疫荧光等实验手段检测其表达差异及对下游炎症相关基因表达调控的改变。结果IRF8野生及突变过表达载体构建成功,且转染效率可观,包装成的慢病毒感染效率亦较高。突变基因IRF8(c.1266dupA)相较于野生型IRF8转录水平降低,表达蛋白的相对分子质量略增大,表达量降低,突变蛋白IRF8mut相对野生型IRF8蛋白核质比增加,IRF8(c.1266dupA)对下游ISRE元件的抑制功能增强。结论IRF8新发移码突变属于功能获得型(gain of function,GOF)突变。 展开更多
关键词 干扰素调节因子8(IRF8) 移码突变 反复感染 转录调控
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UPF1影响AU565乳腺癌细胞侵袭、迁移及EMT的机制
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作者 张金标 苏轲 +2 位作者 徐睿 张天伟 陈冰 《西部医学》 2024年第1期29-35,共7页
目的 探讨上游移码蛋白1(UPF1)对人乳腺癌细胞AU565侵袭、迁移及上皮间充质转化(EMT)的影响及机制研究。方法 收集2021年9月—2022年3月于我院接受乳腺切除术43例乳腺癌患者新鲜癌组织及正常乳腺组织,制备石蜡块,免疫组织化学法检测UPF... 目的 探讨上游移码蛋白1(UPF1)对人乳腺癌细胞AU565侵袭、迁移及上皮间充质转化(EMT)的影响及机制研究。方法 收集2021年9月—2022年3月于我院接受乳腺切除术43例乳腺癌患者新鲜癌组织及正常乳腺组织,制备石蜡块,免疫组织化学法检测UPF1表达情况。购置人乳腺癌细胞系AU565及人乳腺上皮细胞系DU4475,激光共聚焦扫描显微镜法测定UPF1水平。采用小干扰RNA(siRNA)技术构建UPF1低表达的重组细胞,分析转染siRNA-UPF1对AU565细胞侵袭、迁移能力以及EMT相关蛋白表达和蛋白激酶B/哺乳动物雷帕霉素靶蛋白(Akt/mTOR)信号通路的影响。结果 乳腺癌组织UPF1的吸光度值显著高于正常乳腺组织(P<0.05)。AU565细胞UPF1荧光强度显著大于DU4475细胞(P<0.05)。与siRNA-NC组比较,转染siRNA-UPF1后AU565细胞中UPF1蛋白及mRNA表达水平均显著降低(P<0.05)。与siRNA-NC组比较,转染siRNA-UPF1后AU565细胞穿膜率和细胞迁移率均显著增加(P<0.05)。转染siRNA-UPF1后AU565细胞E-candherin蛋白表达水平显著降低,Vimentin和N-cadherin蛋白表达水平显著升高(P<0.05)。转染siRNA-UPF1后AU565细胞p-Akt和p-mTOR水平显著升高(P<0.05)。结论 UPF1在乳腺癌中表达上调,但沉默UPF1可能通过激活Akt/mTOR通路传导,促进乳腺癌细胞AU565的侵袭和迁移,并诱导EMT发生。 展开更多
关键词 乳腺癌 移码蛋白1 侵袭 迁移 上皮间充质转化 蛋白激酶B/哺乳动物雷帕霉素靶蛋白通路
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Novel mutation c.2090_2091del in neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities in an 18.5-mo-old boy:A case report 被引量:1
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作者 Yi Li Zheng Zhou +1 位作者 Yan Xu Zhi-Ru Wang 《World Journal of Clinical Cases》 SCIE 2023年第16期3891-3898,共8页
BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and... BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and functional characteristics of the novel ZMYM2 mutation c.2090_2091del have not yet been reported.CASE SUMMARY The patient was an 18.5-mo-old Chinese boy with motor and language delay,microcephaly,facial dysmorphism,moderate malnutrition,single palmar crease on the left hand,synpolydactyly of the right foot,hypotonia and feeding problems.The boy who was diagnosed with NECRC was enrolled in the First Affiliated Hospital,Henan University of Chinese Medicine,and his clinical data were collected.From the whole-exon sequencing(WES)data,the pathogenic SNVs/InDels were identified,and the molecular findings were characterized.WES revealed that the heterozygous variant in the ZMYM2 gene was c.2090_20-91del,p.Ser697TrpfsTer3,a frameshift mutation,which is a NECRC-related gene mutation.CONCLUSION We performed a systematic literature review to identify and characterize NECRC.Substantial evidence from the literature indicated that patients with ZMYM2 gene mutation showed different degrees of intellectual disability,motor and language retardation,facial dysmorphism,and a few had congenital heart defects,kidney and urinary tract abnormalities.Early diagnosis and prompt management with comprehensive rehabilitation training are beneficial,but may not improve long-term outcomes. 展开更多
关键词 ZMYM2 NECRC frameshift mutation Global developmental delay Case report
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Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome
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作者 Hong-Yang Zhang Chun-Yan Zhang +8 位作者 Fei Wang Hai Tao Ya-Ping Tian Xi-Bin Zhou Fang Bai Peng Wang Jia-Yi Cui Min-Jie Zhang Li-Hua Wang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第4期499-504,共6页
AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundatio... AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene.METHODS:Ophthalmological examinations,including slit-lamp biomicroscopy and lacrimal duct probing,and computed tomography dacryocystography(CT-DCG)were performed for all participants.The family pedigree was drawn,genetic features were analyzed,and the genomic DNA of the subjects was extracted.Pathogenic genes were screened via whole exome sequencing(WES)and confirmed using Sanger sequencing.RESULTS:Six patients belonged to this three-generation family,and their clinical manifestations included congenital nasolacrimal duct obstruction,congenital absence of lacrimal puncta and canaliculi,lacrimal fistulae,and limb deformities.This pattern indicates autosomal dominant inheritance.Diagnosis was based on the clinical characteristics of LADD syndrome,which presented in all the patients in this family.A novel frameshif t mutation in the FGF10 gene(NM_004465.1),c.234dup C(p.Trp79Leus*15),was identified in all patients via WES.The variant was confirmed by Sanger sequencing and classified as a“pathogenic mutation”according to the American College of Medical Genetics and Genomics(ACMG)variant interpretation guidelines.CONCLUSION:A novel frameshift mutation in the FGF10 gene is found in all patients.This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene. 展开更多
关键词 FGF10 gene frameshift mutation congenital lacrimal duct dysplasia LADD syndrome PEDIGREE
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Rett综合征1例病例报道并文献复习
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作者 常倩 丁霞 +3 位作者 周秉博 张巧丽 王凡 尹立琴 《中国医药导报》 CAS 2023年第9期177-180,共4页
报道1例3月龄婴儿因小头畸形、生长发育迟缓行基因高通量测序,结果证实MECP2基因存在移码突变,结合临床表型确诊为Rett综合征的罕见男婴。患儿早期发育正常及发病年龄应大于6月龄不再视为确诊经典Rett综合征的必要条件。该病例报道将为... 报道1例3月龄婴儿因小头畸形、生长发育迟缓行基因高通量测序,结果证实MECP2基因存在移码突变,结合临床表型确诊为Rett综合征的罕见男婴。患儿早期发育正常及发病年龄应大于6月龄不再视为确诊经典Rett综合征的必要条件。该病例报道将为低月龄Rett综合征的诊断提供一定参考,同时提高临床工作者对此病的认识,以期减少误诊及漏诊率。 展开更多
关键词 MECP2突变 移码突变 婴幼儿 RETT综合征
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卵泡蛋白基因的移码突变导致BHD综合征家系的多发性肺囊肿
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作者 褚娇娇 纳建荣 +2 位作者 严梅 尹梅 周玮 《宁夏医学杂志》 CAS 2023年第3期226-228,F0003,共4页
目的Birt-Hogg-Dubé综合征(BHD)是一种常染色体显性遗传病,由卵泡蛋白(FLCN)基因突变引起,其特征以多发肺囊肿、皮肤纤维滤泡瘤和肾肿瘤为表现。方法我们对此家系进行了外显子组测序以确定先证者的致病基因变异,并进行了Sanger测序... 目的Birt-Hogg-Dubé综合征(BHD)是一种常染色体显性遗传病,由卵泡蛋白(FLCN)基因突变引起,其特征以多发肺囊肿、皮肤纤维滤泡瘤和肾肿瘤为表现。方法我们对此家系进行了外显子组测序以确定先证者的致病基因变异,并进行了Sanger测序,以验证先证者和其家系成员的致病突变。同时采用Sanger测序验证了408例与该病无关的汉族健康对照组的突变。结果外显子组测序和Sanger测序分析显示在所有发病的家庭成员中,均存在移码突变(c.1579_1580invA,p.Arg527Glnfs68*)。蛋白印迹检测和免疫组化检测结果显示,该突变导致FLCN蛋白水平显著下降。结论FLCN基因(c.1579_1580invA,p.Arg527Glnfs68*)中的一个移码突变存在于一个仅以多个肺囊肿为表现的BHD综合征家系中;证实了该突变在BHD综合征家系中的致病性。 展开更多
关键词 BHD综合征 多发性肺囊肿 FLCN基因 移码突变
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1例PKD1基因新的插入突变型的发现
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作者 沈婷 刘春艳 《临床肾脏病杂志》 2023年第6期512-514,共3页
常染色体显性多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)是单基因遗传肾病,是临床最为常见,同时也是终末期肾病的常见病因之一,成为肾脏替代治疗的第四大常见病因[1],先前已知的PKD1基因的致病种系突变超过1200个[2]。
关键词 多囊肾病 基因突变 插入突变 移码突变
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基于比较基因组学的解脂亚罗酵母CA20高产赤藓糖醇机理及进化分析
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作者 夏凯 刘芳美 +5 位作者 陈雨晴 陈珊珊 黄春莹 赵学群 沙如意 黄俊 《遗传》 CAS CSCD 北大核心 2023年第10期904-921,共18页
解脂亚罗酵母(Yarrowia lipolytica)是赤藓糖醇生产中使用的主要菌种,复合诱变是选育优良菌株的常用方法。然而,诱变处理所引起的基因组变化尚待探索。本研究对前期获得的高产菌株CA20和原始菌株WT5进行基因组测序,并与已发布的8株解脂... 解脂亚罗酵母(Yarrowia lipolytica)是赤藓糖醇生产中使用的主要菌种,复合诱变是选育优良菌株的常用方法。然而,诱变处理所引起的基因组变化尚待探索。本研究对前期获得的高产菌株CA20和原始菌株WT5进行基因组测序,并与已发布的8株解脂亚罗酵母进行比较基因组分析,旨在探究菌株CA20高产赤藓糖醇的机理以及不同菌株的基因组进化关系。结果显示,菌株CA20基因组大小为20,420,510 bp,GC碱基含量为48.97%,编码6330个CDS和649个ncRNA,菌株CA20和其他8株菌高度同源,平均核苷酸同源性(average nucleotide identity,ANI)>99.50%,其中与菌株IBT 446和H222具有更近的亲缘关系。比较基因组分析显示,CA20和其他8株菌共有5342个核心基因,而CA20特有的65个基因主要参与物质跨膜运输和蛋白质转运过程。CA20基因组中含有166个碳水化合物活性酶(carbohydrate-active enzymes,CAZymes)基因,远多于其他菌株(108~137个),包括特有的4个糖苷水解酶类(glycoside hydrolases,GHs)、2个糖基转移酶类(glycosyltransferases,GTs)和13个碳水化合物酯酶类(carbohydrate esterases,CEs)。除转醛酶TAL1外,赤藓糖醇代谢途径有关酶在不同菌株中高度保守。此外,菌株CA20的赤藓糖醇产量和产率为190.97 g/L和1.33 g/L/h,显著高于WT5的128.61 g/L和0.92 g/L/h(P<0.001)。相比于WT5,CA20中5个基因发生移码变异,15个基因存在非同义突变位点,这些基因主要参与细胞分裂、细胞壁合成、蛋白质合成及稳态维持等过程。以上结果表明,解脂亚罗酵母基因组在进化过程中保守;生存环境不同是导致菌株间基因组差异的重要因素;基因组中CAZymes数量的差异是不同菌株间性能差异的原因之一;菌株CA20高产赤藓糖醇与其细胞结构及内环境稳定性的提升有关。本研究结果为赤藓糖醇高产菌株的定向选育提供基础。 展开更多
关键词 解脂亚罗酵母 赤藓糖醇 比较基因组 移码变异 蛋白激酶
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成年起病-低钙血症-低PTH血症-TBX1移码缺失
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作者 姜悦 杨静 +7 位作者 聂敏 宋桉 王佳佳 姜艳 李梅 夏维波 邢小平 王鸥 《中华骨质疏松和骨矿盐疾病杂志》 CSCD 北大核心 2023年第2期144-150,共7页
甲状旁腺功能减退症(hypoparathyroidism, HP)是一种罕见的内分泌疾病,是由甲状旁腺激素(parathyroid hormone, PTH)合成或分泌缺乏引起的一组临床综合征,其临床特征包括低钙血症、高磷血症、神经肌肉兴奋性增高和软组织异位钙化。本文... 甲状旁腺功能减退症(hypoparathyroidism, HP)是一种罕见的内分泌疾病,是由甲状旁腺激素(parathyroid hormone, PTH)合成或分泌缺乏引起的一组临床综合征,其临床特征包括低钙血症、高磷血症、神经肌肉兴奋性增高和软组织异位钙化。本文报道1例成年起病的HP患者,经基因检测发现TBX1移码缺失(NM_080647,exon3:c.161_186del/p.A54Afs*105),考虑诊断为DiGeorge综合征(DiGeorge syndrome, DGS)相关HP,提示临床医生对患者应进行仔细的体格检查和病史询问,有提示时,即使是成年起病的非手术性HP患者,也应考虑进行相关的基因筛查。 展开更多
关键词 甲状旁腺功能减退症 DIGEORGE综合征 TBX1基因 移码突变
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首次发现1例局灶性节段性肾小球硬化症患儿PAX2基因新的移码变异及文献复习
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作者 李艳 杨焕丹 +4 位作者 周苏芹 朱冰冰 彭倩倩 朱磊 张锐锋 《徐州医科大学学报》 CAS 2023年第11期822-825,共4页
目的了解儿童遗传性慢性肾脏病的临床与病理特点,寻找其致病基因突变位点并分析基因突变与临床表型的关系,以期早期诊断,早期预防。方法收集徐州医科大学附属徐州儿童医院1例疑似为遗传性因素所致慢性肾脏病患儿及其直系亲属的临床资料... 目的了解儿童遗传性慢性肾脏病的临床与病理特点,寻找其致病基因突变位点并分析基因突变与临床表型的关系,以期早期诊断,早期预防。方法收集徐州医科大学附属徐州儿童医院1例疑似为遗传性因素所致慢性肾脏病患儿及其直系亲属的临床资料,并行肾穿刺病理检查,同时采用二代基因测序方法对该患儿、患儿父母及妹妹进行基因检测,寻找可能的突变位点,并与该家系中正常个体进行比较。结果患儿为14岁男孩,3岁时起病,主要临床表现为蛋白尿、夜尿增多,未正规治疗。期间多次尿蛋白++~+++,且逐渐出现尿床症状,家长一直未予重视。2年前于当地医院查肝、肾功能,家长诉未见异常,2019年8月19日因尿床至我院就诊,门诊查尿蛋白+++,血尿素氮13.54 mmol/L,肌酐188μmol/L,肾脏超声提示双肾缩小,肾穿刺活检病理结果为局灶性节段性肾小球硬化症(FSGS)。基因检测示患儿PAX2基因存在c.143delGp.Gly48Valfs*35剪切位点突变,且目前尚未有人群携带记录,因而考虑该患儿为PAX2基因出现新的移码突变。结论该例患儿临床表现为慢性肾脏病,肾活检确诊为FSGS,基因检测PAX2基因发生新的移码变异。对于病因不明的慢性肾脏病患儿应注意完善肾脏病理及基因检测,有助于明确诊断。 展开更多
关键词 儿童 慢性肾脏病 局灶性节段性肾小球硬化症 PAX2基因 移码变异
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