Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.METHODS: Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography (DHPLC) were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles.RESULTS: One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms (77.9%) were diagnosed as colorectal cancer, with an average age of onset at 48.57 ± 29.00 years. Gastric cancer was the most common extracolonic cancer (10.3%) in these families. Twenty-three different sequence variations in hMLH1 and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic.CONCLUSION: Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.     

睑裂狭小综合征一家系病例报告

睑裂狭小综合征（blepharophimosis—ptosis—epican—thus inversus syndrome,BPES）是一种罕见的常染色体显性遗传疾病,亦称先天性小睑裂。我院眼科于2013年8月收治1例,对其进行了家系调查,报告如下。     

2011年7月中国部分法定传染病疫情动态摘抄

流行性腮腺炎河北省：2011年7月报告2165例,报告发病率3.078/10万,无死亡。报告病例数较上月下降20.49%,较2010年同期上升113.72%。报告发病率居前5位的市为承德（8.479/10万）、廊坊（7.013/10万）、张家口（5.404/10万）、石家庄（4.6/10万）及保定（3.019/10万）。广西壮族自治区：2011年7月报告3597例,无死亡。报告病例数较上月上升1.93%,较2010年同期上升47.06%,2011年至本期累计报告数较2010年同期上升41.21%。报告发病数居前5位的县（区）为横县、南宁市西乡塘区、河池市金城江区、贵港市港北区及百色市右江区。     

Clinical characteristics and gene mutation analysis of methylmalonic aciduria

Methylmalonic aciduria（MMA） is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase（MCM,mut complementation group） or in the synthesis of the MCM cofactor adenosylcobalamin（cbl complementation groups）.The defects in the mut complementation group accounts for the largest number of patients with isolated MMA.At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now.This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients.Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry（GC-MS）,and from some of their parents as well.Amplification and direct sequencing of the MUT coding regions（exon 2-13） and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations.In this group,six novel mutations in the MUT gene,c.424A>G（p.T142A）,c.786T>G（p.S262R）,c.808G>C（p.G270R）,c.1323₁324insA,c.1445-1G>A and c.1676+77A>C were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682C>T（p.R228X） and c.323G>A（p.R108H） were also found in this study.In addition,six previously described single nucleotide polymorphism（SNP）,c.636A>G（p.K212K）,c.1495G>A（p.A499T）,c.1595A>G（p.H532R）,c.1992G>A（p.A664A）,c.2011G>A（p.V671I） and c.1677-53A>G were identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.     

t(3;6)染色体平衡易位伴死胎与流产

患者女，结婚10年，怀孕4次，第1胎40天左右人工流产；第2胎为双胎，7个月时，不明原因早产两男婴，两男婴体重分别为1520g和1525g，表型均正常。第1个男婴存活4～5天后死亡，第2个出生时面部发紫，活了4～5小时死亡，死因均不明，未做任何检查；第3胎与第4胎均在怀孕3个月时阴道流血，B超检查妊娠只有30～40天大小，有胎囊，无胎芽，做人工流产。夫妇表型正常，身体健康，非近亲婚配，无有害物品接触史。母亲在怀孕期间有过两次自然流产；其兄结婚有一男孩，其嫂无流产史，家系成员不配合未做任何检查。     

分子医学搏浪蓝海——兼谈基础医学学科发展及教育教学

分子生物学的发展和技术进步为现代遗传学研究奠定了坚实基础。继分子病的概念提出后,人类在病因学和遗传特征与规律等方面对疾病的认知空前深入。在此基础上,分子医学学科体系的建立和研究路径的完善推动了当代医学研究的快速发展。在不断取得突破的同时,分子医学渐渐成为在基础医学领域具有多学科及跨学科兼容性特征的共识性主题。本文结合分子医学的发展历史和对相关文献的综合解析,对国内医学院校基础医学专业在现阶段的发展策略进行思考,归纳出若干关于学科建设和教育教学方略的启示和观点。此外,还针对分子医学在迎接人工智能技术的影响和挑战时所面临的问题进行了初步分析与探讨。     

老年系统性红斑狼疮

系统性红斑狼疮(SLE)是一种特发性自身免疫异常疾病,以育龄期妇女发病为主。SLE被认为是多基因遗传疾病,一些环境因素参与调节相关基因的表达。此外,有证据表明人种起源和年龄影响SLE的表现和临床过程。我国SLE的患病率平均为75／10万,女性高达115／10万。     

健康趣闻

4岁女童患遗传疾病吃不停一生无法独立生活与大多数同龄人一样,英国4岁女童奥利维娅·汤姆林森喜欢吃糖和各种零食,但她的父母却总是不让她吃。她并非受到虐待,而是因为患上遗传疾病,食欲旺盛。父     

Hallervorden-Spatz病1例报告

Hallervorden-Spatz病(HSD)又称苍白球黑质色素变性,是一种罕见的常染色体隐性遗传疾病,1922年由Hallervor-den和Spatz首先报道。我们遇到1例HSD,结合临床资料,报道如下。1临床资料患者,女,52岁。因四肢无力、僵直伴吞咽困难18年入院。18年前无明显诱因出现走路不稳易摔倒,表现为突然     

浅谈产前诊断方法的发展

产前诊断又称宫内诊断或出生前诊断,是指在胎儿出生前用各种方法诊断胎儿是否患有某种遗传病或先天性疾病的一种手段,是人类细胞遗传学、分子遗传学、生物化学和临床医学实践紧密结合的一门学科[1]。胎儿先天性畸形又称胎儿出生缺陷,是指内因与外因共同作用致胚胎发育紊乱引起的形态、结构、功能、代谢、精神、行为等方面的异常,其发生率约占所有新生儿的4％-6％。