一个掌跖角化病家系的调查

本文报道了一个掌跖角化病家系的调查结果．该家系属于弥漫性掌跖角化病,为常染色体显性遗传．     

掌跖角化病41例调查报告

掌跖角化病(keratosis palmaris et plantarls) 是一种较少见的角化过度性遗传病Ll;。我院皮肤科自1980年一1984年所见4例;并对此4 个先证者进行了家族系谱的追访调查;经追访又发现41例发病者（不包括先证者）;兹将调查结果报告如下。     

五个家族货币状掌跖角化病的遗传调查

自Wachters等‘;1983年提出货币状掌跖角化病的命名以来;迄今国内尚未见此病以独立疾病命名报道。作者通过5例先证者追访调查了5个家族;现将调查结果报告如下。     

一罕见的掌跖角化病和胎儿鱼鳞病家系的遗传学研究

掌跖角化病（Keratoderma palmoplantaris）和胎儿鱼鳞病（Ichthyosis Eetalis）均为人类皮肤系统少见的单基因遗传病。在同一家系中这两种遗传病同时出现;而且掌跖角化病已连续遗传 8代;患者达61人之多;胎儿鱼鳞病亦相继出现3例;实属罕见。     

掌跖角化病会遗传吗？

问：我是一名掌跖角化病患者,据父母说4岁开始发病,父母亲都没有此病,上代人也没有此病,我现在27岁了,想咨询一下,此病是否遗传而来？对孩子的遗传几率是多少？该怎么办？     

掌跖脓疱病患者皮损糖皮质激素受体α和β表达的研究

目的：为了解掌跖脓疱病患者皮损中GR表达情况,我们利用免疫组化方法检测患者皮损和正常皮肤标本中GR-α和GR—β的表达,从而探讨其表达在发病中的作用。方法：选择25例临床诊断为掌跖脓疱病患者皮损,26例外科手术切取的健康皮肤作为正常对照。用免疫组化SP法（链酶卵白素-过氧化物酶法）检测掌跖脓疱病患者皮损与正常对照组皮肤GR-α、GR—β的表达数量和强度。结果：两组GR-α表达无显著差异,患者组GR-β表达阳性率及强度明显高于对照组。结论：GR-β在掌跖脓疱病的发病过程中起重要作用。     

掌跖脓疱病患者皮损糖皮质激素受体α和β表达的研究

目的:为了解掌跖脓疱病患者皮损中GR表达情况,我们利用免疫组化方法检测患者皮损和正常皮肤标本中GR-α和GR-β的表达,从而探讨其表达在发病中的作用。方法:选择25例临床诊断为掌跖脓疱病患者皮损,26例外科手术切取的健康皮肤作为正常对照。用免疫组化SP法(链酶卵白素-过氧化物酶法)检测掌跖脓疱病患者皮损与正常对照组皮肤GR-α、GR-β的表达数量和强度。结果:两组GR-α表达无显著差异,患者组GR-β表达阳性率及强度明显高于对照组。结论:GR-β在掌跖脓疱病的发病过程中起重要作用。     

两个亨廷顿舞蹈病家系IT15基因的研究

为了探讨亨廷顿舞蹈病家系患者的临床特征与IT15基因中(CAG)_n重复拷贝数之间的相互关系, 对两家系患者的临床、影像学特征、发病年龄及遗传方式等进行分析; 用聚合酶链反应技术、6%聚丙烯酰胺凝胶电泳及直接测序等方法, 对42名家系成员的IT15基因的(CAG)_n三核苷酸重复序列进行分析。结果显示家系1患者无典型的临床“三联症”及尾状核的萎缩, 18名家系成员中9名患者IT15基因的(CAG)_n拷贝数介于40~50次之间,拷贝数与发病年龄无明显相关; 而家系2患者具有典型的“三联症”和尾状核的萎缩, 24名家系成员中5例患者(CAG)_n拷贝数大于等于50次, 发病年龄与(CAG)_n拷贝数相关。因此亨廷顿舞蹈病患者的临床特征在一定程度上受IT15基因的(CAG)_n三核苷酸重复拷贝数的影响, 拷贝数大于50次, 发病年龄与(CAG)_n拷贝数相关, 并有经父系遗传的(CAG)_n拷贝数的扩展, 且存在遗传早现现象。     

钙泊三醇倍他米松软膏联合NB-UVB对掌跖脓疱病患者血清TNF-alpha, IL-17水平的影响

目的：观察钙泊三醇倍他米松软膏联合窄谱中波紫外线(NB-UVB)治疗掌跖脓疱病的临床疗效及对患者血清肿瘤坏死因子-alpha(TNF-alpha)、白细胞介素-17(IL-17)水平的影响。方法：选取掌跖脓疱病患者63 例,随机分为治疗组和对照组,治疗组外用钙泊三醇倍他米松软膏联合NB-UVB 治疗,对照组单纯照射NB-UVB,两组患者的疗程均为8 周,治疗4 周及8 周后观察临床疗效,并测定血清中TNF-琢、IL-17 的浓度。结果：治疗4周和8 周后,治疗组症状积分较对照组明显下降,差异有统计学意义(P<0.05);治疗4和8 周时,对照组的有效率分别为22.58 %和45.16 %,治疗组为53.13 %和78.13 %,两组患者的有效率比较差异显著(P<0.05);停药后3 个月,对照组复发率为35.48 %,治疗组复发率为12.50 %,治疗组明显低于对照组;治疗后两组患者血清中TNF-alpha、IL-17的浓度均较前下降,且治疗组较对照组下降更明显,差异具有统计学意义(P<0.05)。结论：钙泊三醇倍他米松软膏辅助治疗可以更有效提高掌跖脓疱病患者的临床疗效,且安全性较好,这可能与其降低患者外周血中TNF-琢和IL-17 的水平有关。     

两种高能量超脉冲CO_2点阵激光模式治疗脂溢性角化病的疗效比较与分析

为评价两种高能量超脉冲CO_2激光模式对脂溢性角化病(SK)的治疗效果,本文对81例患者共146处皮损,随机分为A、B两组,每组73处。A组给予超脉冲模式治疗,B组给予点阵模式治疗,观察并对比两组患者疗效、治疗时的疼痛程度、平均治疗次数、痂皮完全脱落时间、遗留红斑消退时间及不良反应。治疗结束后,A、B两组总治愈率分别为100%、95. 89%,差异无统计学意义(P> 0. 05);痂皮完全脱落时间、遗留红斑持续时间、平均治疗次数对比,差异均有统计学意义(P <0. 05);经秩和检验可知,两组患者总不良反应比较,差异有统计学意义(Z=-3. 129,P=0. 002),但进一步单一不良反应间比较,差异均无统计学意义(P> 0. 05)。结果表明,高能量超脉冲CO_2激光点阵模式与超脉冲模式治疗SK均具有较好疗效,但点阵模式创伤小,愈合快,平均治疗次数多,不良反应少,较超脉冲模式更加安全。     

KRT9 gene mutation as a reliable indicator in the prenatal molecular diagnosis of epidermolytic palmoplantar keratoderma

Epidermolytic palmoplantar keratoderma (EPPK) is the most frequent form of such keratodermas. It is inherited in an autosomal dominant pattern and is clinically characterized by diffuse yellowish thickening of the skin on the palms and soles with erythematous borders during the first weeks or months after birth. EPPK is generally caused by mutations of the KRT9 gene. More than 26 KRT9 gene mutations responsible for EPPK have been described (Human Intermediate Filament Database, www.interfil.org), and many of these variants are located within the highly-conserved coil 1A region of the α-helical rod domain of keratin 9. Unfortunately, there is no satisfactory treatment for EPPK. Thus, prenatal molecular diagnosis or pre-pregnancy diagnosis is crucial and benefits those affected who seek healthy descendants. In the present study, we performed amniotic fluid-DNA-based prenatal testing for three at-risk pregnant EPPK women from three unrelated southern Chinese families who carried the KRT9 missense mutations p.Arg163Trp and p.Arg163Gln, and successfully helped two families to bear normal daughters. We suggest that before the successful application of preimplantation genetic diagnosis (PGD), and noninvasive prenatal diagnosis of EPPK that analyzes fetal cells or cell-free DNA in maternal blood, prenatal genetic diagnosis by amniocentesis or chorionic villus sampling (CVS) offers a quite acceptable option for EPPK couples-at-risk to avoid the birth of affected offspring, especially in low- and middle-income countries.     

Identification and analysis of the dog keratin 9 (KRT9) gene

We have identified the gene coding for the canine ortholog of the human keratin 9 protein using the inverse-polymerase chain reaction (PCR) strategy. Sequence comparison and structure analysis of the gene show marked similarity with the human gene. This gene spans about 7 kb and spreads over eight exons. In the dog gene, the reading frame is extended by 20 codons, the first in-frame stop codon being in exon 8 in the dog rather than in exon 7 as in humans. Alignment of human and dog predicted amino acid sequences confirms the high analogy, reaching 75% identity and 95% similarity in the rod domain. Interestingly, the glycine-loop motif number in the C-terminal V2 variable subdomain of the protein increases from 19 in human to 43 in dog, generating a size difference of 12 kDa between the two proteins. Due to its restricted expression pattern in mammalian epidermis, dog keratin 9 gene was a good candidate gene for the genetic palmoplantar hyperkeratosis observed in the Dogue de Bordeaux. However, no polymorphism associated with the pathology was detected within an affected Dogue de Bordeaux pedigree ruling out this hypothesis.     

人KRT2促进体外培养的羊驼皮肤黑色素细胞的黑色素生成

基因表达谱显示,绵羊角蛋白2（keratin2, Krt2）的mRNA在不同毛色皮肤的表达不同,暗示Krt2 基因可能对皮肤黑色素生成有一定的影响。为探索角蛋白2对体外培养的羊驼皮肤黑色素细胞黑色素生成的影响,首先采用PCR扩增产物测序,结合DNAMAN 软件比对分析发现,羊驼Krt2 编码序列（cDNA）与NCBI公布的人KRT2高度同源（91%）;将人KRT2添加于培养的羊驼皮肤黑色素细胞,观察人KRT2对羊驼皮肤黑色素细胞黑色素的生成作用。免疫组织化学显示,外源性的人KRT2处理羊驼皮肤黑色素细胞72 h后,黑色素细胞的细胞质中Krt2表达增强。实时定量PCR及Western 印迹实验揭示,与胎牛血清清蛋白处理的羊驼皮肤黑色素细胞比较,1 ng/mL、10 ng/mL和100 ng/mL人KTR2处理的羊驼皮肤黑色素细胞酪氨酸酶（Tyr）、酪氨酸相关蛋白-1（Tyrp1）、小眼畸形相关转录因子（Mitf）基因表达明显上调（P <0.05）;尤其在添加10 ng/mL KTR2的细胞中,3个基因的mRNA相对表达水平升高尤其显著,分别是对照细胞的4倍、10倍和12.9倍（P<0.01）,蛋白质相对表达水平分别是对照细胞的2倍、2.1倍和1.7倍（P<0.01）。分光光度法测量A490结果证明,1 ng/mL、10 ng/mL和100 ng/mL人KTR2处理的羊驼皮肤黑色素细胞产生的黑色素含量分别是对照细胞的1.3倍（P <0.05）、1.8倍（P <0.01）和1.5倍（P <0.05）。上述结果说明,人KTR2处理可通过刺激羊驼皮肤黑色素细胞黑色素合成相关信号通路,促进黑色素的合成。     

The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 null phenotype by keratin 16.

The type I epidermal keratins K14 and K16 are remarkably similar at the primary sequence level. While a structural function has been clearly defined for K14, we have proposed that a function of K16 may be to play a role in the process of keratinocyte activation that occurs after acute injury to stratified epithelia. To compare directly the functions of the two keratins we have targeted the expression of the human K16 cDNA to the progenitor basal layer of the epidermis of K14 null mice. Mice null for K14 blister extensively and die approximately 2 d after birth (Lloyd, C., Q.C. Yu, J. Cheng, K. Turksen, L. Degenstein, E. Hutton, and E. Fuchs. 1995. J. Cell Biol. 129:1329-1344). The skin of mice expressing K16 in the absence of K14 developed normally without evidence of blistering. However, as the mice aged they featured extensive alopecia, chronic epidermal ulcers in areas of frequent physical contact, and alterations in other stratified epithelia. Mice expressing a control K16-C14 cDNA also rescue the blistering phenotype of the K14 null mice with only a small percentage exhibiting minor alopecia. While K16 is capable of rescuing the blistering, phenotypic complementation in the resulting skin is incomplete due to the multiple age dependent anomalies. Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.