AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate...AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage Ⅲ (48%) and Ⅳ (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/ leucovorin based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys/Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients.展开更多
AIM: To clarify the effects of the xeroderma pigmentosum group D (XPD) Asp312Asn and Lys751Gln gene polymorphisms on the risk of esophageal cancer (EC).
In xeroderma pigmentosum, a rare genodermatosis, transmitted as an autosomal recessive disorder, excessive solar damage to the skin develops at an early age. The disease is characterized by cutaneous, ocular, neurolog...In xeroderma pigmentosum, a rare genodermatosis, transmitted as an autosomal recessive disorder, excessive solar damage to the skin develops at an early age. The disease is characterized by cutaneous, ocular, neurological and oral changes. Oral features in the form of early development of Squamous cell carcinoma, usually at the lower lip and tip of the tongue may be seen. The disorder is associated more commonly in populations where marriage of close blood relatives is common. Treatment of the disorder includes avoidance of Ultra violet radiation, topical application of 5 fluorouracil to treat actinic keratoses, and regular evaluation by an optholmologist, dermatologist, and neurologist. Genetic counseling is an important aspect as an increased incidence of consanguineous marriages have been reported with this disorder. Here, we report an interesting case of xeroderma pigmentosum in an 18 year old male patient who presented with characterstic desquamation of gingiva, fissured tongue and geoghraphic tongue.展开更多
Objective:Xeroderma pigmentosum(XP)is a rare autosomal recessive dermatosis caused by genetic defects of DNA repair.This study was performed to detect and analyze the genes of 2 Uygur patients with XP and their famili...Objective:Xeroderma pigmentosum(XP)is a rare autosomal recessive dermatosis caused by genetic defects of DNA repair.This study was performed to detect and analyze the genes of 2 Uygur patients with XP and their families and assess the patients’phenotypes,which may enrich the understanding of the genetic skin disorder spectrum in Xinjiang area.Methods:We collected the clinical data from 2 patients with XP and peripheral blood samples from the patients and their family members.The patients’DNA was sequenced and detected by Sanger sequencing,and gene mutations were screened.Results:The proband in family 1 presented with brown maculae at the exposure site and squamous cell carcinoma secondary to a facial rash.The proband had a homozygous nucleotide variation of XPC c.2251-2A>G(A change from A to G in the penultimate position of the intron before the 2251 position in the coding region),which was a shear mutation.In this family,both parents were heterozygous,and no similar mutation detected in the sister.In family 2,the proband had scattered black brown spots and papules on the trunk and limbs.and his younger sister was also a patient.The proband and his younger sister had homonucleotide variation of XPA c.631C>T,which was nonsense mutation,resulting in the codon for Arg No.211 being changed into termination codon(p.arg211X),thus terminating the peptide chain synthesis prematurely.All the normal individuals in the two families were heterozygotes,and homozygous mutations occurred in all the patients,which was consistent with the autosomal recessive inheritance.Conclusion:XP is rare in Uygur population.This study expanded the mutation spectrum of XP and provided a basis for early diagnosis,treatment,prognostic prediction,and prenatal genetic consultation.展开更多
Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underly...Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells （iPSCs） harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells （NSCs） or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clari the molecular mechanisms of neurological abnormalities in the XP patients.展开更多
Objective To determine if DNA excision repair enzymes oxoguanine glycosylase 1 （OGG1） and xeroderma pigmentosum group F protein （XPF） are involved in the pathogenesis of Parkinson＇s disease （PD） in a cell model...Objective To determine if DNA excision repair enzymes oxoguanine glycosylase 1 （OGG1） and xeroderma pigmentosum group F protein （XPF） are involved in the pathogenesis of Parkinson＇s disease （PD） in a cell model. Methods PC12 cells were treated with 1-Methyl-4-phenylpyridine ion （MPP＋） for various periods of time to induce oxidative DNA damage. MTT assay was used to determine cell viability. Immunocytochemistry with antibody against 8-hydroxy-2＇- deoxyguanosine （8-oxodG） was used to evaluate oxidative DNA damage. Immunoblotting was used to detect the protein levels of OGG1 and XPF. Results MPP＋ treatment （1 mmol/L） for 18 h and 24 h reduced cell viability to 78.6% and 70.3% of the control, respectively, in a time-dependent way. MPP＋ increased the immunoreactivity of 8-oxodG in the cytoplasm at 3 h and in the nucleus at 24 h of treatment. With the treatment of MPP＋, the expression of OGG1 was significantly increased at 1 h, reaching a peak at 3 h, and then it was decreased at 24 h, as compared to that with vehicle treatment. The same effect was exerted on XPF level, except that the XPF level reached a peak at 18 h of MPP＋ treatment. Moreover, the maximally-increased protein level of OGG1 by MPP＋ was approximately 2-fold higher than that of XPF. Conclusion MPP＋ treatment could time- dependently induce increases in OGG1 and XPF expressions in PC12 cells. Also, this study indicates that the base and nucleotide excision repair pathways may be compensatorily activated in the early stage of pathogenesis in the cells after MPP＋ treatment.展开更多
Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multi...Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the ultraviolet (UV) exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. General features included parental consanguinity (40%), familiarity (60%), onset of symptoms in the first 2 years (50%), malignant skin neoplasms (60%), and carcinoma of the tongue (20%). Among the ocular features, 50% of patients presented with photophobia. Lid freckles or atrophic skin lesions were seen in all patients. Lower lid tumours were seen in 30%, chronic conjunctival congestion in 40%, corneal opacification in 40%, squamous cell carcinoma of limbus in 20%, bilateral pterygium in 40%, and visual impairment in 50%. We report the clinical history and ocular pathology of a boy who is having xeroderma pigmentosum with ocular manifestations. The ophthalmic manifestations of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neuron degeneration of the retina.展开更多
着色性干皮病D组蛋白(Xeroderma pigmentosum group D,XPD)是基础转录因子ⅡH(Transcript factorⅡH,TFⅡH)复合体的第二大亚基,它在转录和核苷酸剪切修复过程中都发挥着重要作用。我们利用人宫颈鳞癌上皮细胞(HeLa细胞)中提取的总RNA...着色性干皮病D组蛋白(Xeroderma pigmentosum group D,XPD)是基础转录因子ⅡH(Transcript factorⅡH,TFⅡH)复合体的第二大亚基,它在转录和核苷酸剪切修复过程中都发挥着重要作用。我们利用人宫颈鳞癌上皮细胞(HeLa细胞)中提取的总RNA进行逆转录酶-聚合酶链反应(Reverse transcriptase-polymerase chain reac-tion,RT-PCR),克隆出人全长XPD cDNA,把此基因按野生型插入表达绿色荧光蛋白的pEGFP-N2质粒,构建了pEGFP-N2/XPD重组体质粒,并将其转染入整合有乙肝病毒X蛋白(Hepatitis B virus X protein,HBx)的人肝癌细胞Hep3B,分析重组细胞的XPD表达水平、HBx表达水平和细胞增殖力,为进一步研究XPD的各种生物学活性及作用机制奠定了基础。展开更多
目的 探讨着色性干皮病G组（xeroderma pigmentosum group G,XPG）基因在不同年龄段健康汉族人群中的表达情况,分析XPG m RNA和蛋白表达量与年龄之间的相关性,以期为法医学年龄推断提供新的分子生物学指标。方法 收集150名不同年龄段健...目的 探讨着色性干皮病G组（xeroderma pigmentosum group G,XPG）基因在不同年龄段健康汉族人群中的表达情况,分析XPG m RNA和蛋白表达量与年龄之间的相关性,以期为法医学年龄推断提供新的分子生物学指标。方法 收集150名不同年龄段健康汉族人的外周血样,采用TRIzol法提取外周血单个核细胞（peripheral blood mononuclear cell,PBMC）总RNA,通过实时荧光定量PCR检测XPG m RNA在PBMC的相对表达量,酶联免疫吸附试验检测XPG蛋白在血浆中的表达量。结果 XPG m RNA及其蛋白表达量在≤18岁组与19~45岁组之间、≤18岁组与≥46岁组之间的差异均有统计学意义（P〈0.05）,但19~45岁组与≥46岁组之间的差异无统计学意义（P〉0.05）。XPG m RNA和蛋白表达量均无性别差异（P〉0.05）。结论 XPG m RNA在PBMC的相对表达量在低龄段内随年龄增加而下降,其血浆中蛋白随年龄增加而升高;XPG基因有望成为法医学年龄推断的新型指标之一。展开更多
背景与目的研究表明DNA损伤修复基因-人类着色性干皮病基因D(xeroderma pigmentosum group D,XPD)多态性与肺癌的易感性有关,但各研究结论不一,本研究拟通过meta分析,定量地评价XPD312和751位点基因多态性与肺癌的关系。方法全面检索相...背景与目的研究表明DNA损伤修复基因-人类着色性干皮病基因D(xeroderma pigmentosum group D,XPD)多态性与肺癌的易感性有关,但各研究结论不一,本研究拟通过meta分析,定量地评价XPD312和751位点基因多态性与肺癌的关系。方法全面检索相关文献,按纳入标准对文献进行筛选后提取相关信息,然后在Stata10软件中按照meta分析流程,选择合适方法计算合并的OR值及95%可信区间,并进行敏感性分析和发表偏倚的估计。结果本研究纳入国内外22篇合格文献,其中XPD312位点15篇,XPD751位点20篇。合并结果显示,携带XPD312Asn/Asn突变基因型患肺癌的危险性是野生型Asp/Asp的1.18倍(95%CI:1.03-1.34,P=0.018);XPD751位点突变基因型也与肺癌危险性升高有关(Lys/GlnOR=1.09,95%CI:1.02-1.18;Gln/GlnOR=1.24,95%CI:1.10-1.41)。亚组分析显示XPD751与肺癌的关联性仅见于欧美人群。漏斗图和Egger’s回归分析均未发现明显的偏倚。结论XPD基因312和751位点的突变与肺癌的易感性升高有关。展开更多
基金Supported by a grant from the Navarra Government 70/2004
文摘AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage Ⅲ (48%) and Ⅳ (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/ leucovorin based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys/Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients.
文摘AIM: To clarify the effects of the xeroderma pigmentosum group D (XPD) Asp312Asn and Lys751Gln gene polymorphisms on the risk of esophageal cancer (EC).
文摘In xeroderma pigmentosum, a rare genodermatosis, transmitted as an autosomal recessive disorder, excessive solar damage to the skin develops at an early age. The disease is characterized by cutaneous, ocular, neurological and oral changes. Oral features in the form of early development of Squamous cell carcinoma, usually at the lower lip and tip of the tongue may be seen. The disorder is associated more commonly in populations where marriage of close blood relatives is common. Treatment of the disorder includes avoidance of Ultra violet radiation, topical application of 5 fluorouracil to treat actinic keratoses, and regular evaluation by an optholmologist, dermatologist, and neurologist. Genetic counseling is an important aspect as an increased incidence of consanguineous marriages have been reported with this disorder. Here, we report an interesting case of xeroderma pigmentosum in an 18 year old male patient who presented with characterstic desquamation of gingiva, fissured tongue and geoghraphic tongue.
文摘Objective:Xeroderma pigmentosum(XP)is a rare autosomal recessive dermatosis caused by genetic defects of DNA repair.This study was performed to detect and analyze the genes of 2 Uygur patients with XP and their families and assess the patients’phenotypes,which may enrich the understanding of the genetic skin disorder spectrum in Xinjiang area.Methods:We collected the clinical data from 2 patients with XP and peripheral blood samples from the patients and their family members.The patients’DNA was sequenced and detected by Sanger sequencing,and gene mutations were screened.Results:The proband in family 1 presented with brown maculae at the exposure site and squamous cell carcinoma secondary to a facial rash.The proband had a homozygous nucleotide variation of XPC c.2251-2A>G(A change from A to G in the penultimate position of the intron before the 2251 position in the coding region),which was a shear mutation.In this family,both parents were heterozygous,and no similar mutation detected in the sister.In family 2,the proband had scattered black brown spots and papules on the trunk and limbs.and his younger sister was also a patient.The proband and his younger sister had homonucleotide variation of XPA c.631C>T,which was nonsense mutation,resulting in the codon for Arg No.211 being changed into termination codon(p.arg211X),thus terminating the peptide chain synthesis prematurely.All the normal individuals in the two families were heterozygotes,and homozygous mutations occurred in all the patients,which was consistent with the autosomal recessive inheritance.Conclusion:XP is rare in Uygur population.This study expanded the mutation spectrum of XP and provided a basis for early diagnosis,treatment,prognostic prediction,and prenatal genetic consultation.
基金This work was supported by National Basic Research Program （973 Program） （Nos. 2015CB964800 and 2014CB910503）, the Strategic Priority Research Program of the Chinese Academy of Sciences （XDA01020312）, National High Technology Research and Development Program of China （2015AA020307）, National Natural Science Foundation of China （Grant Nos. 81330008, 31222039, 31201111, 81371342, 81300261, 81300677, 81271266, 81471414, 81422017, and 81401159）, Beijing Natural Science Foundation （7141005 5142016）, Program of Beijing Municipal Science and Technology Commission （Z151100003915072）, Key Research Program of the Chinese Academy of Sciences （KJZDEW-TZ-L05）, the Thousand Young Talents program of China, National Laboratory of Biomacromolecules （012kf02, 2013kf05, 2013kf11, 2014kf02, 2015kfl 0）. J.C.I.B. was supported by UCAM, the G. Harold and Leila Y. Mathers Charitable Foundation, the Leona M. and Harry B. Helmsley Charitable Trust （2012-PG-MED002） and the Moxie Foundation.
文摘Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells （iPSCs） harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells （NSCs） or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clari the molecular mechanisms of neurological abnormalities in the XP patients.
基金supported by the National Natural Science Foundation of China (No. 30770660,J0730860)
文摘Objective To determine if DNA excision repair enzymes oxoguanine glycosylase 1 （OGG1） and xeroderma pigmentosum group F protein （XPF） are involved in the pathogenesis of Parkinson＇s disease （PD） in a cell model. Methods PC12 cells were treated with 1-Methyl-4-phenylpyridine ion （MPP＋） for various periods of time to induce oxidative DNA damage. MTT assay was used to determine cell viability. Immunocytochemistry with antibody against 8-hydroxy-2＇- deoxyguanosine （8-oxodG） was used to evaluate oxidative DNA damage. Immunoblotting was used to detect the protein levels of OGG1 and XPF. Results MPP＋ treatment （1 mmol/L） for 18 h and 24 h reduced cell viability to 78.6% and 70.3% of the control, respectively, in a time-dependent way. MPP＋ increased the immunoreactivity of 8-oxodG in the cytoplasm at 3 h and in the nucleus at 24 h of treatment. With the treatment of MPP＋, the expression of OGG1 was significantly increased at 1 h, reaching a peak at 3 h, and then it was decreased at 24 h, as compared to that with vehicle treatment. The same effect was exerted on XPF level, except that the XPF level reached a peak at 18 h of MPP＋ treatment. Moreover, the maximally-increased protein level of OGG1 by MPP＋ was approximately 2-fold higher than that of XPF. Conclusion MPP＋ treatment could time- dependently induce increases in OGG1 and XPF expressions in PC12 cells. Also, this study indicates that the base and nucleotide excision repair pathways may be compensatorily activated in the early stage of pathogenesis in the cells after MPP＋ treatment.
文摘Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the ultraviolet (UV) exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. General features included parental consanguinity (40%), familiarity (60%), onset of symptoms in the first 2 years (50%), malignant skin neoplasms (60%), and carcinoma of the tongue (20%). Among the ocular features, 50% of patients presented with photophobia. Lid freckles or atrophic skin lesions were seen in all patients. Lower lid tumours were seen in 30%, chronic conjunctival congestion in 40%, corneal opacification in 40%, squamous cell carcinoma of limbus in 20%, bilateral pterygium in 40%, and visual impairment in 50%. We report the clinical history and ocular pathology of a boy who is having xeroderma pigmentosum with ocular manifestations. The ophthalmic manifestations of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neuron degeneration of the retina.
文摘着色性干皮病D组蛋白(Xeroderma pigmentosum group D,XPD)是基础转录因子ⅡH(Transcript factorⅡH,TFⅡH)复合体的第二大亚基,它在转录和核苷酸剪切修复过程中都发挥着重要作用。我们利用人宫颈鳞癌上皮细胞(HeLa细胞)中提取的总RNA进行逆转录酶-聚合酶链反应(Reverse transcriptase-polymerase chain reac-tion,RT-PCR),克隆出人全长XPD cDNA,把此基因按野生型插入表达绿色荧光蛋白的pEGFP-N2质粒,构建了pEGFP-N2/XPD重组体质粒,并将其转染入整合有乙肝病毒X蛋白(Hepatitis B virus X protein,HBx)的人肝癌细胞Hep3B,分析重组细胞的XPD表达水平、HBx表达水平和细胞增殖力,为进一步研究XPD的各种生物学活性及作用机制奠定了基础。
文摘目的 探讨着色性干皮病G组（xeroderma pigmentosum group G,XPG）基因在不同年龄段健康汉族人群中的表达情况,分析XPG m RNA和蛋白表达量与年龄之间的相关性,以期为法医学年龄推断提供新的分子生物学指标。方法 收集150名不同年龄段健康汉族人的外周血样,采用TRIzol法提取外周血单个核细胞（peripheral blood mononuclear cell,PBMC）总RNA,通过实时荧光定量PCR检测XPG m RNA在PBMC的相对表达量,酶联免疫吸附试验检测XPG蛋白在血浆中的表达量。结果 XPG m RNA及其蛋白表达量在≤18岁组与19~45岁组之间、≤18岁组与≥46岁组之间的差异均有统计学意义（P〈0.05）,但19~45岁组与≥46岁组之间的差异无统计学意义（P〉0.05）。XPG m RNA和蛋白表达量均无性别差异（P〉0.05）。结论 XPG m RNA在PBMC的相对表达量在低龄段内随年龄增加而下降,其血浆中蛋白随年龄增加而升高;XPG基因有望成为法医学年龄推断的新型指标之一。
文摘背景与目的研究表明DNA损伤修复基因-人类着色性干皮病基因D(xeroderma pigmentosum group D,XPD)多态性与肺癌的易感性有关,但各研究结论不一,本研究拟通过meta分析,定量地评价XPD312和751位点基因多态性与肺癌的关系。方法全面检索相关文献,按纳入标准对文献进行筛选后提取相关信息,然后在Stata10软件中按照meta分析流程,选择合适方法计算合并的OR值及95%可信区间,并进行敏感性分析和发表偏倚的估计。结果本研究纳入国内外22篇合格文献,其中XPD312位点15篇,XPD751位点20篇。合并结果显示,携带XPD312Asn/Asn突变基因型患肺癌的危险性是野生型Asp/Asp的1.18倍(95%CI:1.03-1.34,P=0.018);XPD751位点突变基因型也与肺癌危险性升高有关(Lys/GlnOR=1.09,95%CI:1.02-1.18;Gln/GlnOR=1.24,95%CI:1.10-1.41)。亚组分析显示XPD751与肺癌的关联性仅见于欧美人群。漏斗图和Egger’s回归分析均未发现明显的偏倚。结论XPD基因312和751位点的突变与肺癌的易感性升高有关。
