期刊文献+
共找到16篇文章
< 1 >
每页显示 20 50 100
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
1
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
原文传递
Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature 被引量:1
2
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
原文传递
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
3
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
原文传递
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
4
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
下载PDF
Telomere erosion is independent of microsatellite instability but related to loss of heterozygosity in gastric cancer 被引量:35
5
作者 Dian-Chun Fang Shi-Ming Yang Xiao-Dong Zhou Dong-Xu Wang Yuan-Hui Luo Department of Gastroenterology,Southwest Hospital,Third Military Medical University,Chongqing 400038,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第4期522-526,共5页
AIM: To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. METHODS: Telomeric restriction fragment (TRF) length o... AIM: To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. METHODS: Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-betaRII and BAX genes were analyzed by PCR-based methods. RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-betaRII and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (】 or = 2 loci, n = 8), but none was found in those showing low MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and low MSI, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters. No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P【0.01). This tendency was also observed in APC and MCC genes, although there was no statistical significance. CONCLUSION: The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either low MSI or MSS, multiple deletions may represent the LOH pathway. Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer. 展开更多
关键词 ADULT Aged DNA Neoplasm Female Frameshift Mutation Humans Loss of Heterozygosity Male Microsatellite Repeats Middle Aged Research Support Non-U.S. Gov't Stomach Neoplasms TELOMERE
下载PDF
A novel NF1 frame-shift mutation c.703_704delTA in a Chinese pedigree with neurofibromatosis type 1 被引量:6
6
作者 Jun Chen Bo Guo +5 位作者 Min Ren Hong Lin Xin Zhang Si-Yi Chen Xiao-Tian Yu Zhu-Ping Xu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2018年第9期1562-1565,共4页
We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1(NF1). Three members of this family were NF1 patients presenting with different clinical phenotypes and the ot... We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1(NF1). Three members of this family were NF1 patients presenting with different clinical phenotypes and the others were asymptomatic. Exons of NF1 were amplified by polymerase chain reaction, sequenced, compared with a reference database. One novel NF1 frame-shift mutation c.703_704delTA, which resulted in a premature stop signal at codon 720 and the synthesis of truncated, was revealed. This mutation segregated with the NF1 members is likely responsible for the pathogenesis of NF1 in the family. 展开更多
关键词 neurofibromatosis type 1 NF1 gene frameshift mutation
原文传递
A novel frameshift mutation in the beta-subunit of the epithelial sodium channel gene caused Liddle syndrome
7
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
下载PDF
Novelα-galactosidase A gene mutation in a Chinese Fabry disease family:A case report
8
作者 An-Yi Fu Qi-Zhi Jin Ya-Xun Sun 《World Journal of Clinical Cases》 SCIE 2022年第3期1067-1076,共10页
BACKGROUND Fabry disease(FD)is a rare X-linked lysosomal storage disease caused by a deficiency of the enzymeα-galactosidase A.CASE SUMMARY Herein,we analyzed a four-generation Chinese family.The proband is a 57-year... BACKGROUND Fabry disease(FD)is a rare X-linked lysosomal storage disease caused by a deficiency of the enzymeα-galactosidase A.CASE SUMMARY Herein,we analyzed a four-generation Chinese family.The proband is a 57-yearold woman who was diagnosed with left ventricular hypertrophy and atrial fibrillation 7 years ago.Echocardiography showed an end-diastolic diameter of the interventricular septum of 19.9 mm,left ventricular end-diastolic diameter of 63.1 mm,and moderate-to-severe mitral regurgitation.Cardiac magnetic resonance indicated an enlarged left heart and right atrium,decreased left ventricular systolic and diastolic function,a left ventricular ejection fraction of 20%,and thickening of the left ventricular septum.In March 2019,gene and enzyme activity tests confirmed the diagnosis of FD.Her son was diagnosed with FD after gene and enzyme activity assay,and was prescribed agalsidase-βfor enzyme replacement therapy in July 2020.Two sisters of the proband were also diagnosed with FD by genetic testing.Both of them had a history of atrial fibrillation.CONCLUSION A novel mutation was identified in a Chinese family with FD,in which the male patient had a low level of enzyme activity,early-onset,and severe organ involvement.Comprehensive analysis of clinical phenotype genetic testing and enzyme activity testing helped in the diagnosis and treatment of this FD family. 展开更多
关键词 Lysosomal storage disease Enzyme activity Fabry disease Frameshift deletion Whole exon sequencing Case report
下载PDF
Novel mutations of the Alstr?m syndrome 1 gene in an infant with dilated cardiomyopathy:A case report
9
作者 Ping Jiang Liang Xiao +3 位作者 Yuan Guo Rong Hu Bo-Yi Zhang Yi He 《World Journal of Clinical Cases》 SCIE 2022年第7期2330-2335,共6页
BACKGROUND Alstr?m syndrome(AS)is a rare autosomal recessive disease that is generally induced by mutations of the Alstr?m syndrome 1(ALMS1)gene.We report a case of AS,extend the spectrum of ALMS1 mutations and highli... BACKGROUND Alstr?m syndrome(AS)is a rare autosomal recessive disease that is generally induced by mutations of the Alstr?m syndrome 1(ALMS1)gene.We report a case of AS,extend the spectrum of ALMS1 mutations and highlight the biological role of ALMS1 to explore the relationship between dilated cardiomyopathy(DCM)and mutations in ALMS1.CASE SUMMARY We present the case of an infant with AS mainly manifesting with DCM that was caused by a novel mutation of the ALMS1 gene.Whole-exome sequencing revealed a simultaneous large deletion and point mutation in ALMS1,leading to frameshift and missense mutations,respectively,rather than nonsense or frameshift mutations,which have been reported previously.Upon optimized anti-remodeling therapy,biohumoral exams and arrhythmic burden of the infant were alleviated at follow-up after 6 mo.CONCLUSION We identified novel mutations of ALMS1 and extended the spectrum of ALMS1 mutations in an infant with AS. 展开更多
关键词 Alström syndrome Dilated cardiomyopathy Alström syndrome 1 Missense mutation Frameshift mutation Case report
下载PDF
Severe Wolfram Syndrome Caused by a Novel Frameshift Mutation in <i>WFS1</i>Gene: Effect on the WFS1/CaM Interaction and Phenotype-Genotype Correlation
10
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
下载PDF
A loss-of-function mutant allele of a glycosyl hydrolase gene has been co-opted for seed weight control during soybean domestication 被引量:2
11
作者 Siming Wei Bin Yong +7 位作者 Hongwei Jiang Zhenghong An Yan Wang Bingbing Li Ce Yang Weiwei Zhu Qingshan Chen Chaoying He 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2023年第11期2469-2489,共21页
The resultant DNA from loss-of-function mutation can be recruited in biological evolution and development.Here,we present such a rare and potential case of“to gain by loss”as a neomorphic mutation during soybean dom... The resultant DNA from loss-of-function mutation can be recruited in biological evolution and development.Here,we present such a rare and potential case of“to gain by loss”as a neomorphic mutation during soybean domestication for increasing seed weight.Using a population derived from a chromosome segment substitution line of Glycine max(SN14)and Glycine soja(ZYD06),a quantitative trait locus(QTL)of 100-seed weight(q HSW)was mapped on chromosome 11,corresponding to a truncatedβ-1,3-glucosidase(βGlu)gene.The novel gene hsw results from a 14-bp deletion,causing a frameshift mutation and a premature stop codon in theβGlu.In contrast to HSW,the hsw completely lostβGlu activity and function but acquired a novel function to promote cell expansion,thus increasing seed weight.Overexpressing hsw instead of HSW produced large soybean seeds,and surprisingly,truncating hsw via gene editing further increased the seed size.We further found that the core 21-aa peptide of hsw and its variants acted as a promoter of seed size.Transcriptomic variation in these transgenic soybean lines substantiated the integration hsw into cell and seed size control.Moreover,the hsw allele underwent selection and expansion during soybean domestication and improvement.Our work cloned a likely domesticated QTL controlling soybean seed weight,revealed a novel genetic variation and mechanism in soybean domestication,and provided new insight into crop domestication and breeding,and plant evolution. 展开更多
关键词 DOMESTICATION frameshift mutation QTL seed weight SOYBEAN to gain by loss
原文传递
C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting-1 PRF and the NS3 Protein 被引量:1
12
作者 Du Yu Yundi Zhao +4 位作者 Junhui Pan Xingmiao Yang Zhenjie Liang Shengda Xie Ruibing Cao 《Virologica Sinica》 SCIE CAS CSCD 2021年第6期1443-1455,共13页
The Japanese encephalitis serogroup of the neurogenic Flavivirus has a specific feature that expresses a non-structural protein NS1'produced through a programmed-1 ribosomal frameshifting(-1 PRF).Herein,C19orf66,a... The Japanese encephalitis serogroup of the neurogenic Flavivirus has a specific feature that expresses a non-structural protein NS1'produced through a programmed-1 ribosomal frameshifting(-1 PRF).Herein,C19orf66,a novel member of interferon-stimulated gene(ISG)products,exhibited significant activity of antagonizing Japanese encephalitis virus(JEV)infection.Overexpression of C19orf66 in 293T cells significantly inhibited JEV replication,while knock-down of endogenous C19orf66 in HeLa cells and A549 cells significantly increased virus replication.Notably,C19orf66 had an inhibitory effect on frameshift production of JEV NS1'.The inhibition was more significant when C19orf66 and JEV NS1-NS2A were co-expressed in the 293T cells.Both C19orf66-209 and C19orf66-Zinc^(mut) did not significantly change the NS1'to NS1 ratio and had weaker antiviral effects than C19orf66.Similarly,C19orf66-209 and C19orf66-Zinc^(mut) had no significant effect on the expression of the JEV NS3 protein,whose expression was down-regulated by C19orf66 via the lysosome-dependent pathway.These findings suggest that C19orf66 may possess at least two different mechanisms of antagonizing JEV infection.This study identified C19orf66 as a novel interferon-stimulated gene product that can inhibit JEV replication by targeting-1 PRF and the NS3 protein.The study provides baseline information for the future development of broad-spectrum antiviral agents against JEV. 展开更多
关键词 Japanese encephalitis virus(JEV) C19orf66 Programmed-1 ribosomal frameshifting(-1 PRF) NS1’ NS3
原文传递
Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome 被引量:5
13
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
原文传递
Analysis of PAX6 gene in a Chinese aniridia family 被引量:3
14
作者 ZHU Hai-yan WU Ling-qian PAN Qian LIANG De-sheng LONG Zhi-gao DAI He-ping XIA Kun XIA Jia-hui 《Chinese Medical Journal》 SCIE CAS CSCD 2006年第16期1400-1402,共3页
Aniridia is a dominantly inherited eye anomaly characterized by the near or complete absence of the iris with an incidence of approximately 1:80 000.1 Other ocular complications include glaucoma, cataract, and optic ... Aniridia is a dominantly inherited eye anomaly characterized by the near or complete absence of the iris with an incidence of approximately 1:80 000.1 Other ocular complications include glaucoma, cataract, and optic nerve hypoplasia. Aniridia can occur by itself, showing an autosomal dominant inheritance, or as part of the WAGR syndrome (Wilm's tumor, aniridia, genitourinary abnormalities, and mental retardation).2 The PAX6 gene, a transcriptional regulator, is of high homology in many kinds of animal, which involves in ocular morphogenesis3 and responsible for aniridia." It is located on chromosome 11p13 and consists of 14 exons with the initiation codon in exon 4 and the termination codon in exon 13. The PAX6 protein has an unusual structure with two DNA-binding domains, 展开更多
关键词 ANIRIDIA PAX6 frameshift mutation
原文传递
Novel Mutation of Cleidocranial Dysplasia-related Frameshift Runt-related Transcription Factor 2 in a Sporadic Chinese Case 被引量:2
15
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
原文传递
Identification of a novel COL4A5 mutation in the proband initially diagnosed as Ig AN from a Chinese family with X-linked Alport syndrome 被引量:1
16
作者 Zhihui Li Peng Zhu +9 位作者 Hui Huang Ying Pan Peng Han Huanhuan Cui Zhijuan Kang Mai Xun Yi Zhang Saijun Liu Jian Wang Jing Wu 《Science China(Life Sciences)》 SCIE CAS CSCD 2019年第12期1572-1579,共8页
Alport syndrome(AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of... Alport syndrome(AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4 A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence,the proband was initially diagnosed as Ig A nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902 del A in COL4 A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by Ig A nephropathy,which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4 A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis. 展开更多
关键词 Alport syndrome COL4A5 a novel frameshift mutation IgA nephropathy targeted exome-based next-generation sequencing
原文传递
上一页 1 下一页 到第
使用帮助 返回顶部