Background & Aims: The role of the mismatch repair gene PMS2 in hereditary nonpolyposis colorectal carcinoma (HNPCC) is not fully clarified. To date, only 7 different heterozygous truncating PMS2 mutations have be...Background & Aims: The role of the mismatch repair gene PMS2 in hereditary nonpolyposis colorectal carcinoma (HNPCC) is not fully clarified. To date, only 7 different heterozygous truncating PMS2 mutations have been reported in HNPCC-suspected families. Our aim was to further assess the role of PMS2 in HNPCC. Methods: We performed Southern blot analysis in 112 patients from MLH1- , MSH2- , and MSH6- negative HNPCC-like families. A subgroup (n = 38) of these patients was analyzed by denaturing gradient gel electrophoresis (DGGE). In a second study group consisting of 775 index patients with familial colorectal cancer,we performed immunohistochemistry using antibodies against MLH1,MSH2, MSH6, and PMS2 proteins. In 8 of 775 tumors, only loss of PMS2 expression was found. In these cases, we performed Southern blot analysis and DGGE. Segregation analysis was performed in the families with a (possibly) deleterious mutation. Results: Seven novel mutations were identified: 4 genomic rearrangements and 3 truncating point mutations. Three of these 7 families fulfill the Amsterdam II criteria. The pattern of inheritance is autosomal dominant with a milder phenotype compared with families with pathogenic MLH1 or MSH2 mutations. Microsatellite instability and immunohistochemical analysis performed in HNPCC-related tumors from proven carriers showed a microsatellite instability high phenotype and loss of PMS2 protein expression in all tumors. Conclusions: We show that heterozygous truncatingmutations in PMS2 do play a role in a small subset of HNPCC-like families. PMS2 mutation analysis is indicated in patients diagnosed with a colorectal tumor with Absent staining for the PMS2 protein.展开更多
调查数据显示我国现有听力言语残疾人口2780万，占残疾人总数的33％，听力言语残疾者中7岁以下的聋哑患儿高达80万，并以每年新增3万的速度在增长，60岁以上老年人患听力残疾的比例更是高达11％［1］。耳聋的病因复杂，主要分为遗传因...调查数据显示我国现有听力言语残疾人口2780万，占残疾人总数的33％，听力言语残疾者中7岁以下的聋哑患儿高达80万，并以每年新增3万的速度在增长，60岁以上老年人患听力残疾的比例更是高达11％［1］。耳聋的病因复杂，主要分为遗传因素、环境因素以及一些其他不明原因，据估计，遗传因素占耳聋病因的50％以上。根据患者是否伴随其他症状或体征，遗传性聋可分为综合征型聋和非综合征型聋，其中，70％为非综合征型聋（no n -syndromic hearing loss ，NSHL ），30％为综合征型聋（syndromic hearing loss ，SHL）［2］。虽然SHL发病率低于 NSHL ，但由于SHL 患者绝大部分表现为语前聋，除了听力损失外还伴有其他器官系统的疾病，且发病年龄早，表型变化多样，与NSHL相比其遗传背景更为复杂，治疗也更为棘手。本文就常见的常染色体显性遗传性综合征型聋的研究进展以及临床发展情况进行综述。展开更多
文摘Background & Aims: The role of the mismatch repair gene PMS2 in hereditary nonpolyposis colorectal carcinoma (HNPCC) is not fully clarified. To date, only 7 different heterozygous truncating PMS2 mutations have been reported in HNPCC-suspected families. Our aim was to further assess the role of PMS2 in HNPCC. Methods: We performed Southern blot analysis in 112 patients from MLH1- , MSH2- , and MSH6- negative HNPCC-like families. A subgroup (n = 38) of these patients was analyzed by denaturing gradient gel electrophoresis (DGGE). In a second study group consisting of 775 index patients with familial colorectal cancer,we performed immunohistochemistry using antibodies against MLH1,MSH2, MSH6, and PMS2 proteins. In 8 of 775 tumors, only loss of PMS2 expression was found. In these cases, we performed Southern blot analysis and DGGE. Segregation analysis was performed in the families with a (possibly) deleterious mutation. Results: Seven novel mutations were identified: 4 genomic rearrangements and 3 truncating point mutations. Three of these 7 families fulfill the Amsterdam II criteria. The pattern of inheritance is autosomal dominant with a milder phenotype compared with families with pathogenic MLH1 or MSH2 mutations. Microsatellite instability and immunohistochemical analysis performed in HNPCC-related tumors from proven carriers showed a microsatellite instability high phenotype and loss of PMS2 protein expression in all tumors. Conclusions: We show that heterozygous truncatingmutations in PMS2 do play a role in a small subset of HNPCC-like families. PMS2 mutation analysis is indicated in patients diagnosed with a colorectal tumor with Absent staining for the PMS2 protein.
文摘调查数据显示我国现有听力言语残疾人口2780万，占残疾人总数的33％，听力言语残疾者中7岁以下的聋哑患儿高达80万，并以每年新增3万的速度在增长，60岁以上老年人患听力残疾的比例更是高达11％［1］。耳聋的病因复杂，主要分为遗传因素、环境因素以及一些其他不明原因，据估计，遗传因素占耳聋病因的50％以上。根据患者是否伴随其他症状或体征，遗传性聋可分为综合征型聋和非综合征型聋，其中，70％为非综合征型聋（no n -syndromic hearing loss ，NSHL ），30％为综合征型聋（syndromic hearing loss ，SHL）［2］。虽然SHL发病率低于 NSHL ，但由于SHL 患者绝大部分表现为语前聋，除了听力损失外还伴有其他器官系统的疾病，且发病年龄早，表型变化多样，与NSHL相比其遗传背景更为复杂，治疗也更为棘手。本文就常见的常染色体显性遗传性综合征型聋的研究进展以及临床发展情况进行综述。
文摘目的 研究长期接噪人群非镇静听性脑干反应特征及其有效性。方法 选取2023年1月—4月浙江中医药大学医学技术与信息工程学院无长期接噪史的15例青年学生为正常组,另选取杭州祖明豆腐工厂有长期接噪史(接噪时间8 h/d左右)的15例工人为接噪组,两组进行非镇静听性脑干反应,比较两组Ⅰ、Ⅴ波潜伏期及Ⅴ波振幅的差异,采用双变量Pearson相关性分析,探究两组纯音与非镇静ABR的相关性。结果 在80 dB nHL强度下,I波潜伏期正常组潜伏期早于接噪组,差异有统计学意义(P<0.05),其余各强度比较,差异无统计学意义(P>0.05)。两组各强度下V波振幅比较,差异均无统计学意义(P>0.05)。正常组纯音平均阈值与非镇静ABR阈值呈正相关,(r=0.540,P<0.05);接噪组纯音平均阈值与非镇静ABR阈值呈正相关(r=0.688,P<0.01)。结论 在80 dB nHL刺激下Ⅰ波潜伏期延后,对噪声引起的隐性听力损失具有一定的参考价值。接噪组非镇静ABR与纯音测听的相关性高于正常组,两者交叉验证准确性更高。
