COX20基因变异线粒体复合物Ⅳ缺乏症相关的遗传性周围神经病4例病例系列报告及文献复习

背景：原发性线粒体病具有高度的临床和遗传异质性，其中周围神经是线粒体病的常见受累器官之一。 目的：总结COX20基因变异相关周围神经病的临床表型及遗传学特征。 设计：病例系列报告。 方法：回顾性收集2018年5月至2020年5月复旦大学附属儿科医院诊治的COX20基因变异相关周围神经病患儿的临床资料，总结其临床表现、基因检测结果及治疗效果，并以“COX20”、“线粒体复合物Ⅳ缺乏症（Complex Ⅳ deficiency）”为关键词检索中英文数据库。检索时间均为从建库至2021年12月。总结已报道COX20基因变异与临床表型的关系。 主要结局指标：临床表型和COX20基因变异位点。 结果：4例患儿纳入分析，男、女各2例，其中3例自幼运动发育落后。4例均在儿童期起病，均以行走不稳为首发症状。肌电图均提示多发性周围神经损害改变，感觉神经轴索受累为主。4例患儿均携带COX20基因复合杂合变异，包括错义变异2个，无义变异和移码变异各1个，其中移码变异c.262delG(p.E88Kfs*35)尚未见报道。文献复习目前共报道COX基因变异18个家系22例患儿（包括本文病例）,起病中位年龄为5（1.0~17）岁，22例均以行走困难或步态不稳起病，11例（50.0%）有精神运动发育迟滞，病程中14例(63.6%)出现构音障碍，14例(63.6%)出现肌力下降和/或足部畸形，8例（36.4%）出现共济失调，6例(27.3%)出现肌张力障碍，5例（22.7%）存在认知倒退等。21例患儿行神经传导及肌电图检查，19例(90.5%)提示多发性周围神经病变。头颅（18例）及脊髓（10例）MR检查提示，脊髓萎缩4例（40%），小脑萎缩4例（22.2%）。9例患儿已无法独立行走，丧失独立行走能力中位年龄为10（7~21）岁。目前共报道9个变异位点，4种变异类型，其中错义变异5个，剪切变异2个，无义变异和移码变异各1个。 结论：COX20基因变异患者多早期起病，以周围神经系统病变为主要表现，可合并构音障碍、共济失调、肌张力障碍、认知倒退等，病情逐渐进展，致残率高。COX20基因变异类型以错义变异最常见。     

Arg399Gln XRCC1 Polymorphism and Risk of Squamous Cell Carcinoma of the Head and Neck in Jordanian Patients

Background and objective: X-ray repair cross-complementing group1 (XRCC1) is a key protein in base excision repair and closely associated with the coordination of the base excision repair pathway. Many studies have focused on XRCC1 SNPs and have shown an associated between these SNPs and the risk of several types of cancers, including head and neck cancer. There are many single nucleotide polymorphisms XRCC1 gene (SNPs) and the most common SNP that result in amino acid substitutions is exon 10 (Arg399Gln). This study aimed to investigate the association between Arg399Gln SNP and the risk of squamous cell carcinoma of the head and neck. Material and method: Ninety nine patients with squamous cell carcinomas of the head and neck and 89 healthy adult controls were enrolled in this study. The Arg399Gln in XRCC1 allele was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Results: In the single-locus analyses, Arg399Gln SNP showed a significant association with head and neck cancer risk (p value = 0.016 and odd ratio of 1.8). On the genotype level, we applied three analysis models, namely co-dominant, dominant, and recessive genotypes. Arg/Arg homozygous major genotype was significantly (p value <0.05) associated with head and neck squamous cell carcinoma incidence with odd ratio of 2.23 and 2.24 for the co-dominant and recessive models, respectively. Conclusion: The findings indicated that Arg399Gln allele was associated with squamous cell carcinoma of the head and neck among Jordanian patients. This allele might be used as a genetic biomarker of squamous cell carcinoma of the head and neck.     

河南省1例柬埔寨输入登革热病例的病原分子分型与全基因序列分析

目的鉴定河南省1例来自柬埔寨的登革热输入性病例的登革病毒(dengue virus,DENV)血清型和基因型及其序列特征和传播来源。方法患者血液标本来源于2019年国家疾病监测系统网络直报的登革热疑似病例。样品经快速检测DENV NS1抗原和IgM/IgG抗体,再提取血清中核酸,应用荧光RT-PCR法进行DENV血清型鉴定,同时用Vero和BHK-21细胞对血清标本进行病毒分离培养,阳性培养物扩增全基因组序列,进行序列系统进化分析。结果该病例实验室确诊为DENV 1型感染,并从血清标本中分离到病毒株,测序后拼接成全长10670 nt的全基因组序列,经系统进化分析,该病毒株属于DENV 1型基因Ⅰ型,与东南亚流行株具有较高同源性和较近亲缘关系。结论2019年河南省来自柬埔寨的输入性病例的病原体为DENV 1型基因I型,此为近年来东南亚输入我国的常见血清型和基因型。     

基于机器学习的脑胶质瘤多模态影像分析

脑部胶质瘤是临床中常见的一种原发性脑肿瘤，具有复发率高、死亡率高以及治愈率低的特点。常规临床诊断主要依靠计算机断层扫描(CT)和磁共振成像(MRI)检查技术进行鉴别。随着成像技术和机器学习方法的不断发展，多模态影像智能分析技术已经逐步成为研究热点，在脑胶质瘤的病灶分割测量、肿瘤分级、预后生存周期预测和基因型辨别等方面具有重要的应用前景。本文重点介绍基于机器学习和多模态影像在脑胶质瘤临床辅助诊断和预后评估中的应用进展。     

利用基因参照品图谱分析克拉玛依地区HBV基因型

目的了解克拉玛依地区HBV基因型分布状况,比较其与GenBank HBV序列同源性以及进化树分析。方法通过对S基因区B、C、D型GenBank序列分析,研究MboⅠ酶和EarⅠ酶在不同型中具有独特的切点,利用限制性片段多态性分析(PCR_RFLP)区分各型,将各个基因型与GenBank序列进行1∶1同源性比对的进化树分析。结果272份样品有241份成功分型。C型44.8%,B型36.9%,D型4.1%,B C型10.8%,B D型3.3%。少数民族C型40.4%,B型30.7%,D型9.6%。B、C、D型的同源性分别是97.8%~98.7%,96.9%~99.3%,97.5%~99.0%。进化树分析发现,克拉玛依地区的2例D型与新疆哈密地区D型进化距离最近。结论克拉玛依地区HBV基因型B、C、D均有,以B、C型占优势,未检测到A型,D型与新疆哈密地区D型有较近的亲缘关系。     

Creutzfeldt-Jakob病脑组织14-3-3蛋白表达及其意义

目的探讨Creutzfeldt—Jakob病（CJD）脑组织内14-3-3蛋白表达及其诊断意义。方法实验组为5例cJD额叶组织，对照组为4例非CJD额叶组织。采用14-3-3B和s抗体，通过链霉菌抗生物素蛋白-过氧化酶（S—P）免疫组织化学方法进行检测。并参照KB、胶质纤维酸性蛋白（GFAP）、PrP免疫组织化学染色和129基因型检测结果。结果实验组5例脑组织14—3-3蛋白有较多地表达，其中3例灰质与星形胶质细胞尤著。其表达程度与PrP沉积类型有关，而与PrP129基因型无关。对照组4例中除2例急性脑挫伤仅个别神经细胞有表达外，肾上腺脑白质营养不良与额颞叶痴呆灰质和白质均无表达。结论14-3．3蛋白在脑内较多地表达，有利于CJD的病理诊断。     

广州地区小儿乙肝无症状携带者及其父母的HBV DNA基因型研究

目的扩增HBV DNA S基因,建立 HBV DNA的分型方法,研究家庭中小儿乙肝无症状携带者与其父母的基因型.方法利用PCR-RFLP基因分型方法,扩增HBV DNA S基因,以限制性内切酶AvaⅡ,MboⅠ酶切分型;结果 12个家庭共27例乙肝无症状携带者血清,其中两个家庭儿童与父母的基因型相同,均为B型;9个家庭儿童与母亲的基因型相同(7个B型,2个C型),父亲HBV DNA阴性;1个家庭儿童与母亲为B型,父亲为C型,结论本文利用的分型方法经济实用,分型率高,广州地区的基因型以B型,HBV DNA的传播具有家庭聚集性特点及母婴传播的特点.     

肺炎链球菌β-内酰胺酶TEM基因的发现

目的：探讨肺炎链球菌是否产β-内酰胺酶。方法：对2002年9月至2003年4月在苏州大学附属儿童医院就诊的呼吸道感染患儿痰标本中分离到的23株肺炎链球菌进行β-内酰胺酶TEM基因PCR检测与PCR扩增产物直接测序分析。结果：23株肺炎链球菌经TEM基因PCR检测21株阳性，阳性率达91．3％。测得1号菌株(SR001)基因序列为TEM-1型，已登录美国国立生物信息中心，注册号：AY392531。结论：从肺炎链球菌中检出β-内酰胺酶TEM基因。肺炎链球菌对青霉素耐药机制包括产β-内酰胺酶。     

Apolipoprotein E ε4 allele frequency is increased in Parkinson’s disease only with co-existing Alzheimer pathology

We determined the apolipoprotein E (apoE) genotype in clinically diagnosed and neuropathologically verified cases of Parkinson’s disease (PD) (n = 45), with or without Alzheimer (AD)-type changes, and compared the apoE genotype with that in healthy age-matched controls (n = 59). The PD cases were divided into two groups according to the CERAD criteria: “O + A”, with no or only uncertain histological findings of AD, and “B + C” with histological findings suggestive or indicative of AD. DNA was isolated from frozen brain samples, and the apoE genotypes were determined using polymerase chain reaction amplification and subsequent restriction analysis by HhaI enzyme. The frequency of the apoɛ4 allele (29.4%) was significantly increased in the B + C group. The odds ratio for an apoɛ4 allele in the B + C group was 2.5 as compared to controls (95% confidence interval, 1.2–5.2). In the 0 + A group, the frequency of apoɛ4 allele (13.6%) was similar to that in controls (14.4%) and the risk of an apoɛ4 allele was not increased (odds ratio 0.94). The PD cases with an apoɛ4 allele had a greater number of cortical (P = 0.02) but not nigral Lewy bodies than those without an apoɛ4 allele (P = 0.57). The results show that neuropathologically verified PD as such is not associated with increased apoɛ4 allele frequency. Received: 15 January 1998 / Revised, accepted: 24 March 1998     

Specifically associated PCR products probed by coincident detection of two-color cross-correlated fluorescence intensities in human gene polymorphisms of methylene tetrahydrofolate reductase at site C677T: a novel measurement approach without follow-up mathematical analysis

Whole blood samples of known methylene tetrahydrofolate reductase (MTHFR) genotypes from 24 individuals were examined at site C677T. Their amplified DNA products were assessed by two-color fluorescence cross-correlation measurements and agarose gel electrophoresis/capillary gel electrophoresis. DNA subpopulations were identified which were not associated with the proper genotype by primer combinations and cycling conditions called multiplexes. We confirmed that DNA analysis by two-color fluorescence cross-correlation measurements allowed the detection of fluorescence signals specifically associated with the proper genotypes in a mixture of amplified nontarget DNA molecules without DNA sizing. The measurement approach does not require complex, follow-up mathematical analysis and is applicable to any single nucleotide polymorphisms. The simple immunogenetic model showed how the approach works to reveal specific DNA target by preventing detection of nontarget DNA. Under those experimental conditions, a new ultrasensitive, and specific method for clinical immunologists is born.