有汗性外胚层发育不良一家系基因突变

目的 探讨有汗性外胚层发育不良家系的基因突变及突变类型，为建立本病的基因诊断与遗传咨询提供依据。方法 PCR及Sanger测序技术对有汗性外胚层发育不良家系先证者GJB6基因外显子进行突变鉴定，对可疑的变异位点， Sanger测序检测家系其他成员该位点变异情况。结果 基因检测结果表明，家系先症者GJB6基因错义突变c.31G〉A，该突变导致连接蛋白-30（connexin-30, CX-30）第11位氨基酸由甘氨酸变成精氨酸（p.G11R）。家系的患者均携带此变异，而家系表型正常的个体不携带此变异。结论 GJB6基因c.31G〉A（p.G11R）突变是该有汗性外胚层发育不良家系致病基因突变。     

基因诊断有汗性外胚层发育不良一家系

目的 对一个仅有甲和毛发损害的外胚层发育不良家系进行基因突变研究,以期确定其致病基因,明确临床诊断.方法 共收集该家系7例患者及15例正常家系成员外周血,提取基因组DNA,采用PCR扩增候选基因K16、K17、K6a、K6b和GJB6基因的整个编码序列,DNA直接测序明确具体的突变位置和方式,通过RT-PCR在mRNA水平验证该家系的致病基因.结果 家系所有患者GJB6基因均存在一个杂合错义突变31G→A,导致N-末端区域第11位甘氨酸被精氨酸替代(即G11R),而家系中的15例正常人DNA测序结果均未发现此突变.来源于先证者皮损组织的cDNA测序结果亦证实存在该突变.结论 该家系患者均存在GJB6基因突变,此基因为已知的有汗性外胚层发育不良的致病基因.     

X连锁少汗性外胚层发育不良一家系EDA基因的突变

目的检测一X连锁少汗性外胚层发育不良家系的EDA基因突变。方法收集患者及其父母资料,提取外周血DNA,采用PCR扩增EDA基因编码区的全部外显子及其侧翼序列,PCR产物测序,明确突变位点。以50例无关健康人作对照。结果该家系患者第7号外显子第895位鸟嘌呤G突变成腺嘌呤A,使EDA编码的蛋白第299位氨基酸密码子GGC变成AGC,导致正常的甘氨酸被丝氨酸所代替。其母亲在相同位置的碱基出现G-A双峰,显示为杂合性携带者,其父亲及50例无关健康对照未见此改变。结论G299S可能是导致该X性连锁少汗性外胚层发育不良家系临床表型的原因。     

X性连锁少汗性外胚层发育不良家系ED1基因突变检测

目的 探讨X性连锁少汗性外胚层发育不良(XLHED)家系中ED1基因突变。方法 收集2个X性连锁少汗性外胚层发育不良家系外周血标本;采用聚合酶链反应(PCR)结合DNA直接双向测序的方法。结果 家系1中ED1基因的第8个外显子下游与内含子8交界处存在一个新的剪接点缺失突变(IVS8+5 del G)。家系2中第9个外显子处存在一个错义突变(A959G)。这些突变未在两个家系的正常人及188例无关正常对照者中出现。结论 中国人ED1基因突变可引起XLHED,且IVS8+5del G为一个新的突变。     

一遗传性对称性色素异常症家系ADAR基因突变检测

目的 探讨遗传性对称性色素异常症(DSH)一家系ADAR基因突变情况。方法 收集1个遗传性对称性色素异常症家系的外周血标本,采取PCR结合DNA直接测序的方法,检测了该家系中4例患者及3例表型正常者和150例无亲缘关系健康个体的ADAR基因突变情况。结果 该家系中患者存在ADAR基因上第2879位碱基腺嘌呤(A)转换成鸟嘌呤(G),使得ADAR基因的第10号外显子960位密码子由TAT突变成TGT,导致正常的酪氨酸(Tyr)被半胱氨酸(Cys)替代,而该家系的正常人对照及无关健康个体不存在此突变。结论 DSH家系中患者ADAR基因存在错义突变(2879 A→G),这可能是导致DSH发病的分子机制之一。     

应用全外显子测序技术查找有汗性外胚叶发育不良综合征家系致病基因

目的在一个有汗性外胚叶发育不良综合征(hidrotic ectodermal dysplasia,HED)家系中寻找致病基因突变,为该综合征发病的分子机制提供理论依据并为该疾病确诊、产前诊断等奠定分子基础。方法收集所研究的有汗性外胚叶发育不良综合征家系中的2例患者相关临床及病理资料,与家系内正常个体一并采集外周抗凝血血样,利用Illumina Hiseq平台PE150进行外显子测序,结合SAMtool,ANNOVAR分析鉴定并注释患者的突变位点。结果外显子测序结果表明,家系内部所有个体测得2个共有突变,分别为TRPM5(rs80326119,位置:chr11 p15.5)和PTTG1IP(rs143718199,位置:chr21 q22.3),而GJB6处突变A88V(rs28937872)仅为家系内两名有汗性外胚叶发育不良综合征发病患者所共有。结论本研究在有汗性外胚叶发育不良综合征家系中的两名患者中,发现GJB6基因出现A88V突变(rs28937872),从而确证该家系确为有汗性外胚叶发育不良综合征家系;此外,在该综合征家系所有参与外显子测序个体中(包含不患病个体)发现2个共有突变——TRPM5和PTTG1IP;目前,还未见有关两种突变与该病相关联的报道,其与该综合征的关系还有待进一步研究。     

遗传性皮肤病

20 0 4 2 130　 X性连锁少汗性外胚层发育不良家系 ED 1基因突变检测 /陈建军 (合肥医大皮研所 )… //中华皮肤科杂志 .- 2 0 0 3,36 (10 ) .- 553～ 555收集 2个 X性连锁少汗性外胚层发育不良家系外周血标本 ,采用聚合酶链反应结合 DNA直接双向测序的方法检测。结果显示 ,家系 1中 ED1基因的第 8个外显子下游与内含子 8交界处存在一个新的剪接点缺失突变 (IVS8 5del G) ,家系 2中第 9个外显子处存在一个错义突变 (A959G)。这些突变未在两个家系的正常人及 188例无关正常对照者中出现。图 7表 1参 6　(邓翠霞 )2 0 0 4 2 131　遗传性…     

有汗型外胚层发育不良家系调查及基因突变研究

目的：报告1例有汗型外胚层发育不良家系的致病基因突变。方法：收集患者临床资料,提取先证者及其部分亲属外周血DNA进行全外显子测序,Sanger测序验证致病突变。结果：先证者GJB6基因编码区发生杂合无义突变c.263C>T(p.A88V),突变来自其母亲。在其4位患病亲属中检测到相同突变,在其父亲（正常人）中未检测到此突变。结论：GJB6基因c.263C>T(p.A88V)杂合突变是该家系的遗传学致病因素。     

有汗性外胚层发育不良并假阿洪病一例及连接蛋白基因突变检测

目的　对1例有汗性外胚层发育不良并假阿洪病的患者进行了连接蛋白基因突变检测。方法　收集该患者及其正常家属（姐姐）的外周血标本提取总DNA,扩增GJB2、GJB5、GJB6基因的部分编码区序列,双向测序验证基因突变。结果 患者及其姐姐的GJB5、GJB6基因均未检测到突变。在患者GJB2基因检测到2处突变（V27I和V37I）,其姐姐的基因序列未见突变位点。结论　有汗性外胚层发育不良并假阿洪病患者不一定出现GJB6基因突变,可能有别的基因参与致病。     

少汗型外胚叶发育不全新EDA胶原结构域整码缺失突变基因型与表型分析

目的：寻找1例中国汉族少汗型外胚叶发育不全（HED）患者及其核心家系的致病基因。方法：收集1例HED患者及家系资料,采集先证者、核心家系及对照组成员外周血进行全外显子组测序（WES）,采用Sanger测序验证突变基因,对突变EDA位点进行保守性分析,根据《美国医学遗传学与基因组学学会（ACMG）遗传变异分类标准与指南》评估该突变的致病性。结果：先证者中存在一个新的EDA基因突变（参考序列NM＿001399.5）:c.559＿576delCCTCCAGGACCCCCAGGA,该突变导致第187位至第192位氨基酸缺失（p.187＿192del）,为整码缺失突变。患儿母亲同一位置呈现杂合双峰,患儿父亲及对照组未检测到此突变。结论：缺失突变c.559＿576delCCTCCAGGACCCCCAGGA是导致该例HED临床表型的主要原因,该突变位点扩大了EDA基因突变谱。     

Dermatology in private practice in France in 2000

OBJECTIVES: Data regarding French dermatological practice are scarce. Our objective was to identify the skin disorders most commonly diagnosed by office-based dermatologists. We also documented the severity of these skin disorders, as reflected by the repercussions on patient's everyday life, and the way physicians managed patients. DESIGN: We carried out a one-day survey of visits to a randomly selected sample of 900 French office-based dermatologists. The randomization was stratified according to the five French different dialing area codes. RESULTS: Office-based dermatologists saw 6411 patients with 7839 skin disorders during the survey. The daily number of visits to French dermatologists was estimated at 47 000 and the annual number between 12 and 14 millions. Office-based dermatologists mostly managed warts, acne, nevus, dermatitis, malignancies and pre-malignancies, fungal infection and psoriasis. Repercussions on patients'everyday life were assessed by physicians as important or very important in 28 p. 100 of cases. Half of the patients received topical treatment, 20.5 p. 100 a systemic drug and 40 p. 100 a minor surgical procedure (including cryotherapy). CONCLUSION: Although dermatologists frequently see benign skin disorders such as warts or nevus, more severe diseases represent an important part of their activity.     

Pentoxifylline in reactions in leprosy

A study was conducted to assess the response of reactions in leprosy to pentoxifylline therapy. Ten cases were studied; 8 cases had type 2 reaction and 2 cases had type 1 reaction. Pentoxifylline was given orally 400 mg three times daily. In patients with type 2 reaction, good response was observed within one week. There was near complete regression of ENL lesions within one month. Cases with type 1 reaction did not respond to pentoxifylline.     

Leukocyte migration in vivo and in vitro in patients with psoriasis

Leukocyte migration in vivo was studied with a skin chamber technique in 21 patients with active psoriasis vulgaris and 18 with cleared psoriasis vulgaris. Measuring over 24 h, no difference was found between healthy volunteers and most patients with active psoriasis, although a subgroup of patients with long-lasting relapses showed subnormal migration values. In patients with cleared psoriasis on the other hand the in vivo leukocyte migration values were increased. In addition, leukocyte migration in vitro under agarose was studied, but no difference was found between healthy controls and patients with psoriasis, active or cleared.     

Decrease in neutrophils observed in vivo in psoriatics after PUVA therapy

Summary In 56 patients leucocyte and differential counts were done before and at weekly intervals during PUVA treatment of chronic recalcitrant psoriasis. A statistical significant (P<0.01) decrease in the percentage of neutrophils was observed during the first week of the PUVA therapy. This observation could be closely related to the clinical clearing of psoriasis (P=0.02).The effect of PUVA therapy in psoriasis may be due to a decrease in the number of immunocompetent neutrophils demonstrated in psoriatic lesions.