Aim: To identify a gene linking microphthalmia with cyst with early onset medu lloblastoma. Methods: Mutation analysis of the PTCH gene. Results: A mutation in exon 10 of the PTCH genewas identified, confirming a diag...Aim: To identify a gene linking microphthalmia with cyst with early onset medu lloblastoma. Methods: Mutation analysis of the PTCH gene. Results: A mutation in exon 10 of the PTCH genewas identified, confirming a diagnosis ofGorlin syndrom e. Conclusions: This is the first genetically identified mutation giving rise to microphthalmiawith cyst and provides a valuable link in the eye developmental g ene pathway.展开更多
We identified seven novel germline mutations of the PTCH gene in eight unrelat ed Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the P...We identified seven novel germline mutations of the PTCH gene in eight unrelat ed Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplifie d from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations w ere found in all eight patients with NBCCS. The mutations detected in this study include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletio ns, one nonsense mutation and two missense mutations. None of the mutations have been previously reported. Five mutations caused premature stop codons that are predicted to result in a truncated protein. In the two missense mutations, the s trong basic residue arginine was substituted by serine or glycine in highly cons erved components of the putative transmembrane domain of PTCH, and these mutatio ns may therefore affect the conformation and function of the PTCH protein. No ph enotype-genotyperelationshipswerefoundintheJapanese NBCCS patients, consistent with results of previous studies on NBCCS in African-American and Caucasian pat ients.展开更多
目的:探讨PTCH1基因甲基化在胃癌发生中的作用及去甲基化试剂5-氮杂-2′-脱氧胞苷(5-Aza-dC)对胃癌的治疗作用。方法:选取10例胃癌组织及其癌旁正常组织和胃癌细胞株AGS,抽提组织和细胞的总RNA和基因组DNA。实时定量QRT-PCR检测PTCH1基...目的:探讨PTCH1基因甲基化在胃癌发生中的作用及去甲基化试剂5-氮杂-2′-脱氧胞苷(5-Aza-dC)对胃癌的治疗作用。方法:选取10例胃癌组织及其癌旁正常组织和胃癌细胞株AGS,抽提组织和细胞的总RNA和基因组DNA。实时定量QRT-PCR检测PTCH1基因的mRNA表达,MSP(methylation specific PCR)分析PTCH1基因启动子区甲基化变化。用5-Aza-dC处理AGS细胞株,流式细胞术检测细胞周期和凋亡并观察PTCH1基因甲基化水平的改变。结果:胃癌组织、癌旁正常组织和胃癌细胞株AGS中PTCH1基因表达和启动子甲基化水平呈负相关,相关系数为-0.591(P=0.006);5-Aza-dC的处理可引起胃癌细胞AGS细胞发生凋亡和G0/G1期阻滞,PTCH1基因发生去甲基化变化并表达增加。结论:PTCH1基因启动子区高甲基化是胃癌细胞PTCH1低表达主要原因之一,5-Aza-dC能逆转PTCH1基因甲基化状态,调控其表达,对胃癌具有一定的治疗作用。展开更多
文摘Aim: To identify a gene linking microphthalmia with cyst with early onset medu lloblastoma. Methods: Mutation analysis of the PTCH gene. Results: A mutation in exon 10 of the PTCH genewas identified, confirming a diagnosis ofGorlin syndrom e. Conclusions: This is the first genetically identified mutation giving rise to microphthalmiawith cyst and provides a valuable link in the eye developmental g ene pathway.
文摘We identified seven novel germline mutations of the PTCH gene in eight unrelat ed Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplifie d from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations w ere found in all eight patients with NBCCS. The mutations detected in this study include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletio ns, one nonsense mutation and two missense mutations. None of the mutations have been previously reported. Five mutations caused premature stop codons that are predicted to result in a truncated protein. In the two missense mutations, the s trong basic residue arginine was substituted by serine or glycine in highly cons erved components of the putative transmembrane domain of PTCH, and these mutatio ns may therefore affect the conformation and function of the PTCH protein. No ph enotype-genotyperelationshipswerefoundintheJapanese NBCCS patients, consistent with results of previous studies on NBCCS in African-American and Caucasian pat ients.
文摘目的探讨PTCH1基因rs28 377 268位点多态性与骨质疏松性椎体压缩骨折患者骨代谢标志物的关系。方法选取2016年1月至2016年6月我科脊柱组收治的骨质疏松性椎体压缩骨折患者(骨折组)和脊柱退行性病变骨质疏松患者(对照组)各80例。采用SNa Pshot法进行SNP分型,化学发光法测定骨代谢标志物:骨钙素(osteocalcin,OC)、Ⅰ型胶原羧基端肽β特殊序列(beta-crosslaps of type I collagen cross-linked C-telopeptide,β-CTX)、Ⅰ型前胶原氨基端前肽(procollagen I N-terminal propeptide,P1NP)、25-羟维生素D(25-hydroxyvitamin D,25(OH)D)、甲状旁腺激素(parathyroid hormone,PTH)浓度。比较两组等位基因频率、基因型频率分布及两组骨代谢标志物浓度差异,并分析PTCH1基因rs28 377 268位点多态性与骨代谢标志物浓度的关系。结果骨折组和对照组G、T等位基因频率均为80%、20%,两组GG、GT、TT基因型频率分别为66.25%、27.50%、6.25%和62.50%、35.00%、2.50%,无统计学意义(P>0.05)。骨折组中血清OC、PINP、β-CTX及25(OH)D浓度较对照组均无统计学意义,而PTH浓度明显高于对照组(P<0.05)。血清OC、PINP、β-CTX及25(OH)D浓度在GG、GT、TT3种基因型之间亦无统计学意义(P>0.05),血清PTH浓度在GT、TT基因型中均高于GG基因型,其中TT基因型显著高于GG、GT基因型(P<0.05)。结论 PTCH1基因rs28 377 268位点在骨质疏松患者中G、T等位基因的表达频率分别为80%、20%,rs28377268-T等位基因高表达可能间接升高血清PTH浓度,促进骨质疏松发生,增加椎体脆性骨折风险。
文摘目的:探讨PTCH1基因甲基化在胃癌发生中的作用及去甲基化试剂5-氮杂-2′-脱氧胞苷(5-Aza-dC)对胃癌的治疗作用。方法:选取10例胃癌组织及其癌旁正常组织和胃癌细胞株AGS,抽提组织和细胞的总RNA和基因组DNA。实时定量QRT-PCR检测PTCH1基因的mRNA表达,MSP(methylation specific PCR)分析PTCH1基因启动子区甲基化变化。用5-Aza-dC处理AGS细胞株,流式细胞术检测细胞周期和凋亡并观察PTCH1基因甲基化水平的改变。结果:胃癌组织、癌旁正常组织和胃癌细胞株AGS中PTCH1基因表达和启动子甲基化水平呈负相关,相关系数为-0.591(P=0.006);5-Aza-dC的处理可引起胃癌细胞AGS细胞发生凋亡和G0/G1期阻滞,PTCH1基因发生去甲基化变化并表达增加。结论:PTCH1基因启动子区高甲基化是胃癌细胞PTCH1低表达主要原因之一,5-Aza-dC能逆转PTCH1基因甲基化状态,调控其表达,对胃癌具有一定的治疗作用。
