●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven fa...●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were recruited.All family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.622C>T(p.Arg208Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia.This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.展开更多
Objective： Cervical cancer （CC） is the second most common type of cancer in women worldwide, after breast cancer. High-risk human papillomaviruses （HR-HPVs） are considered to be the major causes of cervical cance...Objective： Cervical cancer （CC） is the second most common type of cancer in women worldwide, after breast cancer. High-risk human papillomaviruses （HR-HPVs） are considered to be the major causes of cervical cancer. HPV16 is the most common type of HR-HPVs and HPV16 E6 gene is one of the major oncogenes. Specific mutations are considered as dangerous factors causing CC. This study was designed to find mutations of HPV16 E6 and the relationship between the mutations and the happening of CC. Methods： The tissue DNA was extracted from 15 biopsies of CC. Part of HPV16 E6 gene （nucleotide 201-523） was amplified by polymerase chain reaction （PCR） from the CC tissue DNA. The PCR fragments were sequenced and analyzed. Results： The result of PCR showed that the positive rate of HPV16 E6 was 93.33% （14/13）. After sequencing ana analyzing, in the 13 out of 14 PCR fragments, 4 maintained prototype （30.77%）, 8 had a same 350G mutation （61.54%）, and 1 had a 249G mutation （7.69%）. Conclusion： This study suggest that there is a high infection rate of HPV in cervical cancer and most of the HPV16 E6 gene has mutations. Those mutations may have an association with the development of cervical cancer.展开更多
AIM: To investigate the mutations of the 5' noncoding region of BCL-6 gene in Chinese patients with primary gastric lymphomas.METHODS: PCR and direct DNA sequencing were used to identify BCL-6 gene mutations in th...AIM: To investigate the mutations of the 5' noncoding region of BCL-6 gene in Chinese patients with primary gastric lymphomas.METHODS: PCR and direct DNA sequencing were used to identify BCL-6 gene mutations in the 5' noncoding region in 29 cases of gastric diffuse large B-cell lymphoma (DLBCL)and 18 cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma as well as 10 cases of reactive hyperplasia of lymph node (LRH).RESULTS: Six of 29 gastric DLBCLs (20.7%), 4 of 18 gastric MALT lymphomas (22.2%) and 1 of 10 LRHs(10%) were found to have mutations. All mutations were single-base substitutions and the frequency of single-base changes was 0.20x10-2-1.02x10-2 per bp.CONCLUSION: Point mutations in the 5' noncoding region of BCL-6gene are found in Chinese patients with primary gastric DLBCLs and MALT lymphomas, suggesting that they may, in some extent, participate in the pathogenesis of primary gastric DLBCLs and MALT lymphomas.展开更多
Background and aim: The Krüppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of...Background and aim: The Krüppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity (LOH). However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas (HCCs). We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines. Methods: We analyzed the exon-2 of KLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting. Results: KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression of KLF6 mRNA or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild-type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1-S transition by inducing the expression of p21WAF1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects. Conclusion: Our findings suggest that KLF6 may be involved in pathogenesis of HCC.展开更多
BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There ...BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There are few case reports and genetic analyses,especially of KDM6A gene mutation,in China.CASE SUMMARY This study reports a de novo KDM6A mutation in a Chinese infant with KS.A 2-month-old Chinese baby was diagnosed with KS,which manifested as hypoglycemia,congenital anal atresia at birth,feeding difficulties,hypotonia,and serious postnatal growth retardation.He died of recurrent respiratory infections at age 13 mo.DNA sequencing of his blood DNA revealed a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19).CONCLUSION We present a Chinese KS patient with a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19),broadening the mutation spectrum.展开更多
AIM:To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies(CD) in 8 Chinese probands.· METHODS:Eight unrelated patients with stromal corneal dystrophies were recr...AIM:To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies(CD) in 8 Chinese probands.· METHODS:Eight unrelated patients with stromal corneal dystrophies were recruited in this study;all affected members were assessed by completely ophthalmologic examinations.Genomic DNA was extracted from peripheral leukocytes,17 exons of TGFBI gene and the exon of CHST6 gene were amplified by polymerase chain reaction(PCR),sequenced directly and compared with the reference database.· RESULTS:Three heterozygous mutations in TGFBI gene were identified in six patients:c.370C>T(p.Arg124Cys) was found in exon 4 of TGFBI gene in three members,c.371G>A(p.Arg124His) was found in one patient;c.1663C>T(p.Arg555Trp) was found in exon 12 in other two members.In addition,four polymorphisms with the nucleotide changes rs1442,rs1054124,rs4669,and rs35151677 were found in TGFBI gene.Mutations were not identified in the rest of 2 affected individuals in TGFBI gene or CHST6 gene.· CONCLUSION:Within these patients,R124C,R124H and R555W mutations were co-segregated with the disease phenotypes and were specific mutations for lattice corneal dystrophy type I(LCD I),Avellino corneal dystrophy(ACD,GCDⅡ),granular corneal dystrophy type I(GCD I),respectively.Our study highlights the prevalence of codon 124 and codon 555 mutations in the TGFBI gene among the Chinese stromal corneal dystrophies patients.·展开更多
选择性先天缺牙是由遗传或环境因素导致的牙齿数目异常,多累及恒牙列。低密度脂蛋白受体相关蛋白6(low-density lipoprotein receptor-related protein 6,LRP6)是选择性先天缺牙的常见致病基因之一,该基因突变为常染色体显性遗传,可导...选择性先天缺牙是由遗传或环境因素导致的牙齿数目异常,多累及恒牙列。低密度脂蛋白受体相关蛋白6(low-density lipoprotein receptor-related protein 6,LRP6)是选择性先天缺牙的常见致病基因之一,该基因突变为常染色体显性遗传,可导致非综合征型先天缺牙或综合征型先天缺牙;非综合征型先天缺牙仅表现为牙齿数目、形态异常;综合征型先天缺牙可表现为耳部发育畸形、口面裂、毛发稀少、汗腺异常等。笔者就近年来关于LRP6基因突变导致选择性先天缺牙的表型及基因突变特点的研究现况进行综述,文献收纳24个LRP6基因突变位点和38例相关先天缺牙患者,发现LRP6基因突变导致的选择性先天缺牙好发于上颌侧切牙及上下颌第二前磨牙和第一前磨牙,极少发生于第一磨牙,尤其是下颌第一磨牙,未见上颌中切牙缺失。LRP6基因在牙发育过程中主要通过WNT/β-catenin信号通路发挥重要作用,LRP6基因突变可导致蛋白表达和功能异常、信号通路破坏从而导致选择性先天缺牙。现有文献结果显示,LRP6基因突变好发于胞外段E1、E2亚结构域,影响WNT/β-catenin信号通路的传导而致病。然而目前对于选择性先天缺牙仍缺乏成熟完善的对因治疗。展开更多
This study sought to analyze the genotype and gene mutations of human seizure-related gene 6 in 98 patients with idiopathic generalized epilepsy （non-febrile seizures）, who were selected from three generations of th...This study sought to analyze the genotype and gene mutations of human seizure-related gene 6 in 98 patients with idiopathic generalized epilepsy （non-febrile seizures）, who were selected from three generations of the Chinese Han population living in Shanghai, Zhejiang Province, Wuxi of Jiangsu Province, and Jiangxi Province of Southern China. Twenty-six patients＇ parents were available as a first-degree relatives group and 100 biologically unrelated healthy controls were collected as the control group. Based on the age of onset and seizure type, the patients were divided into six subgroups. Polymerase chain reaction and DNA direct sequencing analysis showed that the most frequent mutations c. 1249dupC （p.Gly418Argfx31 ） and c.1636A 〉 G （p.Thr546Ala） were detected in some idiopathic generalized epilepsy patients and tl^eir asymptomatic first-degree relatives （30.6% vs. 19.2% and 11.2% vs. 26.9%）. A novel mutation c.1807G 〉A （p.Val603Met） was found in a patient with late-onset idiopathic generalized epilepsy. There was no significant difference in the incidence of these three mutations among the different subgroups of idiopathic generalized epilepsy and controls. Thus, further analysis of a larger population is needed to confirm the assumption that human seizure-related gene 6 is a susceptibility gene for idiopathic generalized epilepsy with various sub-syndromes.展开更多
Human papillomavirus 16 (HPV-16) is a major high-risk type causing cervical cancer. The E6 and E7 genes in HPV-16 are the major virulent genes in HPV, and we wanted to investigate the polymorphism of E6 and E7 genes o...Human papillomavirus 16 (HPV-16) is a major high-risk type causing cervical cancer. The E6 and E7 genes in HPV-16 are the major virulent genes in HPV, and we wanted to investigate the polymorphism of E6 and E7 genes of HPV-16 originated from Jingjiang, Jiangsu province. In research, HPV-16 sample was collected, and the E6 and E7 genes fragments were amplified by PCR assay. The sequences of E6 and E7 genes were used for phylogenetic analysis by Mega 5.0 software. By comparison, the major mutations of E6 gene were T178G (41.67%) and G658A (17%), as well as C58G, T61A and G188C (14%), T61C and C656A (11%). The mutation of E7 gene was mainly C491A and T935A (23%);G514C, G937C and G519C (11%). The 68 nucleotide site deficiency (69.4%) of E6 and 535 nucleotide site deficiency (23%) of E7 were dominant. In our study, we did not find the relevance between the E6 and E7 genes mutations and pathologic severity. But we think the E6 and E7 genes mutation of HPV-16 might affect vaccine prevention and treatment effect.展开更多
文摘●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were recruited.All family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.622C>T(p.Arg208Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia.This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.
基金supported by a grant from the 11th Five-year Plan Medical Science Fundation of PLA (No06MA084)
文摘Objective： Cervical cancer （CC） is the second most common type of cancer in women worldwide, after breast cancer. High-risk human papillomaviruses （HR-HPVs） are considered to be the major causes of cervical cancer. HPV16 is the most common type of HR-HPVs and HPV16 E6 gene is one of the major oncogenes. Specific mutations are considered as dangerous factors causing CC. This study was designed to find mutations of HPV16 E6 and the relationship between the mutations and the happening of CC. Methods： The tissue DNA was extracted from 15 biopsies of CC. Part of HPV16 E6 gene （nucleotide 201-523） was amplified by polymerase chain reaction （PCR） from the CC tissue DNA. The PCR fragments were sequenced and analyzed. Results： The result of PCR showed that the positive rate of HPV16 E6 was 93.33% （14/13）. After sequencing ana analyzing, in the 13 out of 14 PCR fragments, 4 maintained prototype （30.77%）, 8 had a same 350G mutation （61.54%）, and 1 had a 249G mutation （7.69%）. Conclusion： This study suggest that there is a high infection rate of HPV in cervical cancer and most of the HPV16 E6 gene has mutations. Those mutations may have an association with the development of cervical cancer.
基金Supported by National Natural Science Foundation of China,No.39900065
文摘AIM: To investigate the mutations of the 5' noncoding region of BCL-6 gene in Chinese patients with primary gastric lymphomas.METHODS: PCR and direct DNA sequencing were used to identify BCL-6 gene mutations in the 5' noncoding region in 29 cases of gastric diffuse large B-cell lymphoma (DLBCL)and 18 cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma as well as 10 cases of reactive hyperplasia of lymph node (LRH).RESULTS: Six of 29 gastric DLBCLs (20.7%), 4 of 18 gastric MALT lymphomas (22.2%) and 1 of 10 LRHs(10%) were found to have mutations. All mutations were single-base substitutions and the frequency of single-base changes was 0.20x10-2-1.02x10-2 per bp.CONCLUSION: Point mutations in the 5' noncoding region of BCL-6gene are found in Chinese patients with primary gastric DLBCLs and MALT lymphomas, suggesting that they may, in some extent, participate in the pathogenesis of primary gastric DLBCLs and MALT lymphomas.
文摘Background and aim: The Krüppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity (LOH). However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas (HCCs). We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines. Methods: We analyzed the exon-2 of KLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting. Results: KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression of KLF6 mRNA or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild-type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1-S transition by inducing the expression of p21WAF1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects. Conclusion: Our findings suggest that KLF6 may be involved in pathogenesis of HCC.
文摘BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There are few case reports and genetic analyses,especially of KDM6A gene mutation,in China.CASE SUMMARY This study reports a de novo KDM6A mutation in a Chinese infant with KS.A 2-month-old Chinese baby was diagnosed with KS,which manifested as hypoglycemia,congenital anal atresia at birth,feeding difficulties,hypotonia,and serious postnatal growth retardation.He died of recurrent respiratory infections at age 13 mo.DNA sequencing of his blood DNA revealed a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19).CONCLUSION We present a Chinese KS patient with a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19),broadening the mutation spectrum.
文摘AIM:To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies(CD) in 8 Chinese probands.· METHODS:Eight unrelated patients with stromal corneal dystrophies were recruited in this study;all affected members were assessed by completely ophthalmologic examinations.Genomic DNA was extracted from peripheral leukocytes,17 exons of TGFBI gene and the exon of CHST6 gene were amplified by polymerase chain reaction(PCR),sequenced directly and compared with the reference database.· RESULTS:Three heterozygous mutations in TGFBI gene were identified in six patients:c.370C>T(p.Arg124Cys) was found in exon 4 of TGFBI gene in three members,c.371G>A(p.Arg124His) was found in one patient;c.1663C>T(p.Arg555Trp) was found in exon 12 in other two members.In addition,four polymorphisms with the nucleotide changes rs1442,rs1054124,rs4669,and rs35151677 were found in TGFBI gene.Mutations were not identified in the rest of 2 affected individuals in TGFBI gene or CHST6 gene.· CONCLUSION:Within these patients,R124C,R124H and R555W mutations were co-segregated with the disease phenotypes and were specific mutations for lattice corneal dystrophy type I(LCD I),Avellino corneal dystrophy(ACD,GCDⅡ),granular corneal dystrophy type I(GCD I),respectively.Our study highlights the prevalence of codon 124 and codon 555 mutations in the TGFBI gene among the Chinese stromal corneal dystrophies patients.·
文摘选择性先天缺牙是由遗传或环境因素导致的牙齿数目异常,多累及恒牙列。低密度脂蛋白受体相关蛋白6(low-density lipoprotein receptor-related protein 6,LRP6)是选择性先天缺牙的常见致病基因之一,该基因突变为常染色体显性遗传,可导致非综合征型先天缺牙或综合征型先天缺牙;非综合征型先天缺牙仅表现为牙齿数目、形态异常;综合征型先天缺牙可表现为耳部发育畸形、口面裂、毛发稀少、汗腺异常等。笔者就近年来关于LRP6基因突变导致选择性先天缺牙的表型及基因突变特点的研究现况进行综述,文献收纳24个LRP6基因突变位点和38例相关先天缺牙患者,发现LRP6基因突变导致的选择性先天缺牙好发于上颌侧切牙及上下颌第二前磨牙和第一前磨牙,极少发生于第一磨牙,尤其是下颌第一磨牙,未见上颌中切牙缺失。LRP6基因在牙发育过程中主要通过WNT/β-catenin信号通路发挥重要作用,LRP6基因突变可导致蛋白表达和功能异常、信号通路破坏从而导致选择性先天缺牙。现有文献结果显示,LRP6基因突变好发于胞外段E1、E2亚结构域,影响WNT/β-catenin信号通路的传导而致病。然而目前对于选择性先天缺牙仍缺乏成熟完善的对因治疗。
基金supported by Shanghai Natural Science Foundation, China, No. ZR1404500
文摘This study sought to analyze the genotype and gene mutations of human seizure-related gene 6 in 98 patients with idiopathic generalized epilepsy （non-febrile seizures）, who were selected from three generations of the Chinese Han population living in Shanghai, Zhejiang Province, Wuxi of Jiangsu Province, and Jiangxi Province of Southern China. Twenty-six patients＇ parents were available as a first-degree relatives group and 100 biologically unrelated healthy controls were collected as the control group. Based on the age of onset and seizure type, the patients were divided into six subgroups. Polymerase chain reaction and DNA direct sequencing analysis showed that the most frequent mutations c. 1249dupC （p.Gly418Argfx31 ） and c.1636A 〉 G （p.Thr546Ala） were detected in some idiopathic generalized epilepsy patients and tl^eir asymptomatic first-degree relatives （30.6% vs. 19.2% and 11.2% vs. 26.9%）. A novel mutation c.1807G 〉A （p.Val603Met） was found in a patient with late-onset idiopathic generalized epilepsy. There was no significant difference in the incidence of these three mutations among the different subgroups of idiopathic generalized epilepsy and controls. Thus, further analysis of a larger population is needed to confirm the assumption that human seizure-related gene 6 is a susceptibility gene for idiopathic generalized epilepsy with various sub-syndromes.
文摘Human papillomavirus 16 (HPV-16) is a major high-risk type causing cervical cancer. The E6 and E7 genes in HPV-16 are the major virulent genes in HPV, and we wanted to investigate the polymorphism of E6 and E7 genes of HPV-16 originated from Jingjiang, Jiangsu province. In research, HPV-16 sample was collected, and the E6 and E7 genes fragments were amplified by PCR assay. The sequences of E6 and E7 genes were used for phylogenetic analysis by Mega 5.0 software. By comparison, the major mutations of E6 gene were T178G (41.67%) and G658A (17%), as well as C58G, T61A and G188C (14%), T61C and C656A (11%). The mutation of E7 gene was mainly C491A and T935A (23%);G514C, G937C and G519C (11%). The 68 nucleotide site deficiency (69.4%) of E6 and 535 nucleotide site deficiency (23%) of E7 were dominant. In our study, we did not find the relevance between the E6 and E7 genes mutations and pathologic severity. But we think the E6 and E7 genes mutation of HPV-16 might affect vaccine prevention and treatment effect.
