播散性浅表性光化性汗孔角化症MVK基因突变检测

目的：研究2个中国汉族播散性浅表性光化性汗孔角化症（DSAP）家系患者MVK基因突变。方法：提取2个DSAP家系及1 0 0 名无亲缘关系的健康对照外周血DNA,采用PCR扩增患者MVK基因的全部外显子及其侧翼序列,用Sanger测序法对PCR扩增产物直接测序检测基因突变。结果：发现1 个新的剪切位点突变（c.1040-2A>C）和1 个已报道的错义突变（c.1094T>C）。结论：本研究进一步证实MVK基因突变与DSAP发病相关。     

斑块型汗孔角化症一家系MVK基因突变检测

目的：检测1家系7例中国汉族斑块型汗孔角化症（PM）患者MVK基因上的突变位点。方法：收集家系成员7例患者及3名正常成员的临床资料及血液样本,提取外周血DNA,PCR技术扩增MVK全部外显子及其侧翼序列,并采用Sanger测序法对纯化后的PCR产物进行检测。并将检测结果与既往测得676例健康对照的全部外显子进行对比。结果：在7例患者中检测出突变位点（c.604G>A）,此突变曾在播散性浅表性光化性汗孔角化症（DSAP）患者中报道。正常家系成员及健康对照中未检测到此突变。结论：本家系中MVK基因突变（c.604 G>A）与PM发病有关,且为DSAP与PM的共同突变位点。     

汗孔角化症三例散发患者基因突变分析

目的:检测3例散发汗孔角化症患者的致病基因突变。方法:提取3例患者外周血进行基因组DNA提取，通过高通量测序检测患者的突变基因，再用Sanger测序验证。结果:3例汗孔角化症均存在MVD基因突变，患者1检测到c.875A>G(p.Asn292Ser)突变，患者2、3检测到(c.746 T>C)(p.Phe249Ser)突变。结论:本研究再次验证MVD基因为汗孔角化症常见突变。     

外显子测序联合体细胞突变检测发现汗孔角化症八个突变位点

目的:外显子测序联合体细胞突变检测发现新的汗孔角化症致病基因突变.方法:收集前期实验在已知基因上通过目标区域测序未发现突变的29例汗孔角化症患者的外周血DNA进行全外显子测序,并提取体细胞DNA进行Sanger测序.结果:通过全外显子测序,在3例患者外周血DNA中检出剪切位点突变,包含1个MVK基因上的新突变位点.通过...     

播散性浅表性光化性汗孔角化症MVK基因突变分析

目的:检测12例中国汉族播散性浅表性光化性汗孔角化症（DSAP）患者MVK基因突变位点。方法:对中国汉族6个家系和6个散发DSAP患者及100名无亲缘关系的健康对照血样,提取外周血DNA,PCR扩增样本MVK基因的全部外显子及其侧翼序列,Sanger测序法对PCR扩增产物进行测序。结果:在2个家系和1例散发患者中分别检测到c.566C>T,c.722G>T和c.207₂08delAC突变位点。结论:MVK基因与DSAP的发病有关。     

播散性浅表性光线性汗孔角化症1例致病突变位点的鉴定及功能初探

目的 对播散性浅表性光线性汗孔角化症的突变位点进行鉴定并初步探讨其功能。方法 对患者的外周血进行采样,收集全基因组DNA,采用PCR结合Sanger测序验证突变位点。构建野生型和突变型5-焦磷酸甲羟戊酸脱羧酶(MVD)相关真核表达载体,通过免疫印迹法检测MVD相关突变对蛋白在细胞中溶解度的影响。结果 测序发现,MVD cDNA,c.746T>C是该患者的致病位点,此突变属于播散性浅表性光化性汗孔角化症的热点突变。功能研究发现该突变导致MVD蛋白在细胞中的溶解度改变,具体表现为野生型MVD主要存在于上清中,突变导致MVD蛋白以不可溶的状态存在于细胞沉淀中。结论 本研究鉴定了该患者发病的遗传突变,证实了既往已报道过的突变位点,进一步表明MVD为播散性浅表性光线性汗孔角化症的致病基因,突变导致蛋白的溶解度降低可能是该病发病的原因之一。     

4例可变性红斑角化症的基因突变检测

目的:检测4例可变性红斑角化症患者的基因突变位点.方法:应用DNA直接测序法检测基因的突变.结果:发现1个新的突变位点,1个已报道突变位点.结论:错义突变c.403C＞G和c.292C＞T是导致该3例患者发生可变性红斑角化症的特异突变.     

汗孔角化病2例及文献复习

报告2例汗孔角化病。例1.患者女，57岁，面部、颈部及四肢斑块渐增多30年。皮肤科检查：面部、颈部及四肢等暴光部位可见圆形、花环状或不规则的角化过度斑，边缘隆起，中央轻度凹陷、萎缩。诊断：播散性浅表性光线性汗孔角化病。例2.患者男，45岁，全身散在斑块20年余。皮肤科检查：全身散在棕褐色角化性斑块，部分边缘隆起，纤细如线，离心性扩大，中央色素沉着。诊断：播散性浅表性汗孔角化病。2例皮损组织病理检查均可见角化不全柱斜插入凹陷的表皮内。全外显子测序发现相关突变，例1为MVK c.1126G>A，例2为ATP2C1 c.899+4A>T。     

GJB2基因p.N54H突变致经典型Vohwinkel综合征1例

目的检测1例表现为掌跖角化、假性阿洪及耳聋的Vohwinkel综合征患者的基因变异。方法采集先证者临床信息, 并检测分析基因突变位点。结果先证者临床表现符合经典型Vohwinkel综合征, 基因检测发现GJB2基因c.160A>C(p.N54H)杂合突变, 患者父母及健康对照均未发现此位点变异。结论 GJB2基因c.160A>C(p.N54H)突变首次被发现与经典型Vohwinkel综合征相关, 经典型Vohwinkel综合征及掌跖角皮症伴耳聋之间存在变异位点重叠。     

播散性浅表性光化性汗孔角化症SLC17A9基因突变分析

目的：检测11例山东汉族播散性浅表性光化性汗孔角化症SLC17A9基因突变位点。方法：提取患者外周血DNA,采用PCR扩增患者SLC17A9基因的全部外显子及其侧翼序列,对PCR扩增产物直接测序检测。结果：11例DSAP患者的SLC17A9基因编码区的所有外显子均未发现突变。结论：本研究中11例DSAP患者的发病与SLC17A9基因的编码区序列无关。     

异维A酸治疗播散性浅表性光线性汗孔角化症

患者女,68岁。全身散在褐色角化性丘疹伴瘙痒2年余。皮损组织病理检查示角化过度,表皮增生,柱状角化不全,部分角化不全柱下可见部分角化不良细胞,真皮浅层片状淋巴细胞浸润。全基因组外显子测序提示患者MVK基因突变。诊断:播散性浅表性光线性汗孔角化症,治疗:口服异维A酸软胶囊、抗组胺药和外用维A酸药物3个月余,皮疹逐渐消退,瘙痒缓解,目前患者仍在随访中。     

Carvajal综合征一例伴桥粒斑蛋白基因新突变

【摘要】 目的 对1例临床表现为羊毛状发,膝盖、掌跖角化性皮损,暂无心脏症状的患儿进行基因突变检测。方法 收集患儿及其父母的临床资料。提取患儿、其父母及100例无关健康对照者外周血DNA,采用二代皮肤靶向测序包检测患儿的基因突变,应用Sanger测序法进行验证。结果 患儿女,3岁,出生头发卷曲,8月龄出现掌跖角化并渐累及膝盖,其父母表型正常。测序发现,患儿桥粒斑蛋白（DSP）基因第23号外显子存在移码突变c.5152dupT（p.L1718Ffs*15）,DSP基因第24号外显子检测到无义突变c.C6478T（p.R2160X）。其母亲DSP基因第23号外显子亦存在c.5152dupT移码突变,但第24号外显子未检测到相关突变。其父亲及100例健康对照中均未检测到相关突变。诊断：Carvajal综合征。结论 该例Carvajal综合征患儿存在DSP基因复合杂合突变c.5152dupT（p.L1718Ffs*15）和c.C6478T（p.R2160X）,可能与其发病有关。     

Disseminated Superficial Porokeratosisin a Patient with Gastric Cancer

Disseminated superficial porokeratosis (DSP) is a rare variant of porokeratosis, which is characterized histologically by cornoid lamella and clinically by central atrophy with elevated borders. DSP is usually associated with immunosuppressive states and hematopoietic malignancies, but rarely with malignancies of visceral organs. A 65-year-old male presented with numerous brownish macules with elevated borders on the trunk and limbs that had been present for 1 year. Before the visit to our clinic, gastric cancer was diagnosed at about the same time the skin lesions suddenly increased in size and number. Clinical and histopathological examination revealed that the lesions were consistent with DSP. We herein report a rare case of disseminated superficial porokeratosis that occurred in association with gastric cancer.     

Disseminated superficial porokeratosis and immunosuppression

We present a patient who developed skin lesions typical of disseminated superficial porokeratosis (DSP) while on immunosuppressive therapy for pemphigus foliaceus. Phototesting with artificial light sources did not have any effect on the DSP lesions. The literature describing occurrence of DSP on immunosuppression is reviewed and possible pathogenetic mechanisms are discussed.     

Porokeratosis in Singapore: an Asian perspective

Porokeratosis is a rare disorder of skin keratinisation characterised by a cornoid lamella. We reviewed its associations with immunosuppression and phototherapy, as well as the risks of malignant progression. This is a retrospective review on all cases of porokeratosis seen at the National Skin Centre, Singapore, between 2000 and 2010. A total of 94 patients were reviewed. Clinical and histological diagnoses were confirmed in 63% patients. Most patients were Chinese (89%) with a mean age of 51.6 years. The male to female ratio was 1.4:1. The four main clinical variants were classical porokeratosis of Mibelli (56%), disseminated superficial actinic porokeratosis (DSAP) (18%), disseminated superficial porokeratosis (DSP) (11%), and linear porokeratosis (13%). Phototherapy-induced porokeratosis, seen in three patients, is rare. Seven cases of porokeratosis occurred in patients who were immunosuppressed. Progression of porokeratosis to malignancy is uncommon and was observed in three patients. The most common treatments included cryotherapy (26.5%) as well as topical steroids or retinoids (38.1%). A good response, defined as clear or almost clear lesions, occurred in 16% patients. The most common presentation of porokeratosis in our review was a middle-aged male patient with an asymptomatic lesion of porokeratosis of Mibelli over the extremities. No particular immunosuppressive drug was implicated. Porokeratosis associated with ultraviolet phototherapy or malignancy is rare. Progression of porokeratosis to malignancy arose in the disseminated variants, with a possible correlation with age. This is the largest institutional retrospective review of porokeratosis to date and highlights the major epidemiological characteristics of this condition.     

A promoter sequence variant of ZNF750 is linked with familial psoriasis

We previously mapped a psoriasis-susceptibility gene to a 3.8-Mb region of the 17q terminus in a five-generation Chinese family with autosomal-dominant psoriasis. To identify the mutations responsible for the psoriasis in this family, we sequenced 78 genes within the region and found four gene variants, p.Ala201Val in CD7, c.-625A>C in zinc-finger protein 750 (ZNF750), p.Asp189Asn in C17orf56, and p.Ala568Thr in AATK cosegregated with the disease. The latter two variants were not studied further in the absence of disease segregation in other familial psoriasis and presence of variants in normal subjects. Functional analyses of CD7 did not support CD7 as a disease-causing gene. In contrast, the c.-625A>C mutation in ZNF750 resulted in a 42% reduction of the promoter activity, and the electrophoretic mobility shift assay showed binding of nuclear protein(s) to the mutant C allele. The c.-625A>C mutation was found in another sporadic psoriasis patient but was absent in 188 normal controls. Together, the mutation accounts for 1.7% (confidence interval: 0.2-5.84%) of psoriasis in the Chinese population. This report suggests that ZNF750 mutations could contribute to psoriasis susceptibility.     

Disseminated superficial porokeratosis: what is the association with ultraviolet radiation?

A female patient is presented w ho consistently developed lesions of disseminated superficial porokeratosis (DSP) whilst on holiday abroad. The lesions resolved completely within 4–6 weeks of return to the UK. Induction of the lesions by exposure to artificial sources of UVA and UVB was unsuccessful.