KRT5基因新突变(p.Gly207Asp)导致一家系伴斑状色素沉着的单纯性大疱性表皮松解症

目的:对伴斑状色素沉着的单纯性大疱性表皮松解症一家系进行KRT5和KRT14致病基因突变筛查.方法:提取家系中每一位成员的DNA样本,应用聚合酶链式反应(PCR)扩增KRT5和KRT14基因编码区及外显子-内含子交界区,对PCR产物进行DNA测序.选择100例正常人群作为对照组,将突变结果在The Genome Agg...     

伴斑点状色素沉着的单纯性大疱性表皮松解症1例国内首报

患儿男,15岁。躯干、四肢反复发生水疱和大疱,伴色素沉着和色素减退15年。皮损组织病理示:棘层下部棘细胞间裂隙和陈旧性表皮内水疱,部分基底细胞液化或空疱变性及基底层色素增加,真皮血管周围多数淋巴和嗜酸粒细胞浸润。直接免疫荧光检查阴性。透射电镜下超微结构示角质形成细胞间水肿,基底细胞内裂隙和空泡形成,并见大量张力微丝排列为均质化团块,部分呈漩涡状;基底细胞及细胞间可见黑素小体。诊断:单纯性大疱性表皮松解症,斑点状色素沉着。经云南省医学信息研究所查证证实该例为国内首例报道。     

角蛋白14突变导致Dowling-Meara亚型单纯型大疱性表皮松解症伴色素沉着

目的:检测Dowling-Meara 亚型单纯型大疱性表皮松解症(DM-EBS)伴色素沉着一家系的基因突变.方法:收集DMEBS患儿临床资料;取皮损行透射电镜检查;应用PCR及DNA 直接测序的方法,检测该家系成员角蛋白(KRT)5 和KRT14 基因的全部编码序列,并与正常序列进行对比.结果:透射电镜检查可见基底细胞下部裂隙形成,张力微丝呈团块状.患儿KRT14基因第1 号外显子中的第373 位碱基发生C→T 杂合突变(c.C373 T),导致其编码的KRT14 1A 螺旋段第125 位氨基酸发生错义突变(p.R125C),患儿父母未发现该突变.结论:KRT14 基因的R125C 突变可能为引起该患儿临床表型的病因,推测认为该突变不仅可引起表皮松解,还可造成皮肤色素沉着.     

两个家系单纯型大疱性表皮松解症Weber—Cockayne亚型的基因 …

目的 鉴定更我的单纯型大疱性表皮松解症（ＥＢＳ）突变以研究ＥＢＳ基因型和表型关系,为ＥＢＳ的遗传咨询及基因诊断和基因治疗奠定基础,方法 应用聚合酶链反应、单链构象多态性和ＤＮＡ直接测序明确基因突变位点和突变方式,结果 家系Ⅰ角蛋白Ｋ１４Ｌ１２区存在Ｖ２６８Ｄ错义突变,家系Ⅱ角蛋白Ｋ５Ｌ１２区存在Ｎ３２９Ｓ错义突变,结论 进一步证明Ｋ５／Ｋ１４的Ｌ１２区是许多ＥＢＳ－Ｗｅｂｅｒ－Ｃｏｃｋａｙｎｅ突变     

KRT5基因新生突变致重度型单纯型大疱性表皮松解症一家系

目的:报道1例重度型单纯型大疱性表皮松解症,并检测其基因突变。方法:收集患者及其父母资料和外周血,提取基因组DNA,全外显子组测序筛查患儿致病基因,随后采用Sanger测序对家系成员进行验证。结果:患者KRT5基因第7号外显子第1 429位碱基发生G→A（c.1429G>A）杂合突变,导致KRT5基因所编码的蛋白第47...     

获得性大疱性表皮松解症1例

获得性大疱性表皮松解症（epiderrnolysis bullosa acquisita EBA)是一种自身免疫性表皮下大疱病，以摩擦或外伤部位出现张力性水疱及血清内存在高滴度胶原自身抗体为基本特征，本病临床较少见，且临床表现和其他大疱性皮肤病类似，较易引起误诊，现将本科诊治的1例报告如下。     

PCR—DNA直接测序检测1例单纯型大疱性表皮松解症Weber—Cockay…

单纯型大疱性表皮松解症（ＥＢＳ）是一组常染色体显性的遗传性疾病，研究表明本病存在角蛋白Ｋ５／Ｋ１４基因点突变。ＥＢＳ的各个亚型突变发生部位有一定差异，其中Ｗｅｂｅｒ－Ｃｏｃｋａｙｎｅ亚型（ＷＣ－ＥＢＳ）突变多位于Ｋ５／Ｋ１４的连接区Ｌ１－２。本研究设计了扩增Ｋ５基因Ｌ１－２区ＤＮＡ片段的引物，应用ＰＣＲ对－ＷＣ－ＥＢＳ家系的患者及未发病成员进行扩增。ＰＣＲ产物测序发现患者Ｋ５第３４６密码子发生了Ａ     

获得性大疱性表皮松解症伴肝硬化腹水死亡1例

患者,男,５４岁,因双手足、四肢伸侧、骶部散在水疱、渗液、结痂、疤痕１３年伴纳差、腹胀８月余入院。患者自１９８４年１２月份因外伤左手腕部出现黄豆大水疱,疱破后糜烂、渗液,几日后自行结痂,渐肘、膝、骶部等易摩擦处均出现水疱,疱易破,渗液粘稠,结痂处愈合后遗留萎缩性疤痕。曾在上海华山医院病理检查后诊为“获得性大疱性表皮松解症”,间断服用过强的松３０—４０ｍｇ／日,以及支持治疗（白蛋白、能量合剂、各种维生素）,病情时轻时重。近８月来突觉纳差、腹胀,偶伴恶心、呕吐,呕吐为非喷射性,同时伴吞咽困难。并出现…     

胫前大疱性表皮松解症一例

患者女,35岁,因双小腿胫前皮肤红色丘疹,水疱伴瘙痒20年来我院就诊,患者15岁时无明显诱因出现双小腿皮肤瘙痒,搔抓或轻度碰撞,摩擦后易出现水疱,水疱糜烂结痂痊愈后留有瘢痕样红色丘疹。在正常皮肤或陈旧皮损表面可出现新皮损,病情迁延不愈,皮疹渐增多并蔓延至膝部及肘部,期间患者曾在多家医院诊治,曾诊断为湿疹,结节性痒疹,皮肤淀粉样变等,     

隐性遗传营养不良性大疱性表皮松解症1例

患者男，17岁，因全身复出现水疱糜烂伴瘙痒17年，于2003年5月22日收住我院。其父诉患者出生时左小腿伸侧大片皮肤缺失。40d后皮肤表面反复出现水疱，大疱，疱易破，约1周后可自行愈合。疱多发生在肘膝关节伸侧，颈部，腋下等易受摩擦的部位。冬轻夏重。随着年龄的增长发作程度及频率有所下降。父母非近亲结婚，其妹体健，家族中无类似患者。     

Epidermolysis Bullosa Simplex with Mottled Pigmentation: A Family Report and Review

Abstract: Epidermolysis bullosa simplex with mottled hyperpigmentation (EBS‐MP) is an uncommon subtype of EBS. Its clinical features depend on the age of diagnosis, and clinical variations have been described even within family members. We present six cases from two unrelated Spanish families each with several affected members with EBS‐MP and review the clinical and genetic findings in all reported patients. We highlight the changing clinical features of the disease throughout life.     

Epidermolysis Bullosa Simplex Herpetiformis of Dowling-Meara with Mottled Pigmentation: The Relationship Between EBS Herpetiformis and EBS with Mottled Pigmentation

Abstract: A 6–year-oid girl with epidermolysis bullosa simplex (EBS) is described. Clinical features include generalized herpetiform blistering of the skin, healing without scars, intraoral blistering, nail dystrophy, palmo-plantar keratoderma, and improvement with age. An unusual feature was the presence of a striking mottled pigmentation involving the arms, trunk, and legs. Histology, immunofluorescence, and electron microscopy of a fresh lesion showed an intraepidermal split within the basal kerati-nocytes, focal hyperpigmentation of the basal cells without an inflammatory infiltrate, and tonofilament clumping. Our patient illustrates the clinical features of Dowling-Meara EBS with the pigmentary changes of EBS with mottled pigmentation. The relationship between EBS of Dowling-Meara and EBS with mottled pigmentation is discussed.     

Molecular confirmation of the unique phenotype of epidermolysis bullosa simplex with mottled pigmentation

BACKGROUND: A distinctive subtype of epidermolysis bullosa simplex, with the additional feature of mottled pigmentation (EBS-MP), was initially characterized in a Swedish family in 1979, and seven further families have been reported. Features of EBS-MP that are observed in most affected patients include acral blistering early in childhood, mottled pigmentation distributed in a number of sites, focal punctate hyperkeratoses of the palms and soles, and dystrophic, thickened nails. The genetic basis of EBS-MP has been ascribed in five unrelated families to a heterozygous point mutation, P25L, in the non-helical V1 domain of K5. OBJECTIVES: We report a clinical, ultrastructural and molecular study of two of the earliest families to be clinically characterized as EBS-MP. METHODS: The P25L mutation was identified in all affected members of each of these families, bringing the total number of EBS-MP families with this mutation to seven. RESULTS: This unusual recurrent mutation may uniquely cause EBS-MP. CONCLUSIONS: While the exact molecular mechanisms by which this mutation causes epidermolysis, palmoplantar keratoderma and pigmentation remain elusive, we suggest possible molecular mechanisms through which the P25L substitution could cause this unusual phenotype.     

先天性大疱性鱼鳞病样红皮病一例KRT1及KRT10基因突变检测

目的：对先天性大疱性鱼鳞病样红皮病一例散发患者进行KRT1及KRT10基因的突变分析。方法：收集临床资料,提取外周血DNA,采用PCR技术扩增KRT1及KRT10基因的编码区及侧翼序列,用Sanger法测序检测潜在的基因突变,选取与患者无亲缘关系的100名健康人作为对照。结果：该患者KRT10检测出第1号外显子中第467位碱基发生G→A杂合突变（c.467G>A）,导致其编码的第156号氨基酸发生错义突变（p.R156H）。患者父母及正常对照均未发现该突变。KRT1基因未检测到突变。结论：KRT10基因的错义突变c.467G>A可能与该患者发病有关。     

Evaluation of an Avidin-Biotin-Peroxidase Method with a Monoclonal Antibody to Type IV Collagen in the Differential Diagnosis of Bullous Pemphigoid and Epidermolysis Bullosa Acquisita

There are reports in which an immunohistochemical technique with a monoclonal antibody to type IV collagen has been employed for differentiating between bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA). The aim of this study was to determine whether this method could be used routinely. Biopsies (paraffin-embedded lesional skin containing a blister) from currently diagnosed patients with clinical features suggesting BP or EBA were examined by an avidin-biotin-peroxidase (ABC) technique. Sera were tested by indirect immunofluorescence on salt-split skin (IF) and immunoblotting (IB). In all cases which exhibited clear type IV collagen staining, the results of the ABC technique agreed with results of both IF and IB. In one confirmed EBA case, it was impossible to unequivocally localize type IV collagen, because it stained very faintly. Taking into consideration the results of our study, data indicating that the level of blistering might not coincide with the localization of immunoreactants in EBA cases and the possibility of an enzymatic destruction of lamina densa, we conclude that the ABC method is unsuitable for differentiation between BP and EBA.     

A Case of Non-Hallopeau-Siemens Recessive Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa (DEB) is a rare group of heritable mechanobullous disorders that are characterized by blistering and scarring of the skin and mucosae and these lesions are induced by minor trauma, DEB is also associated with nail dystrophy. DEB can be inherited either in an autosomal recessive or dominant fashion. Regardless of the mode of inheritance, DEB is caused by defects of the ultrastructural entity known as the anchoring fibril, which results in separation of the sublamina densa. Recessive DEB (RDEB) is classified into Hallopeau-Siemens and non-Hallopeau-Siemens. We herein report on a case of non-Hallopeau-Siemens RDEB and there was no family history of this malady, and we present the clinical, histological and electron microscopy findings.     

痒疹样营养不良型大疱性表皮松解症误诊1例

患者女,46岁。反复双下肢结节、水疱13年,加重伴泛发全身2年。先后在各地多家医院进行了4次组织病理检查,诊断为"痒疹、扁平苔藓"等。躯干背部、肘关节、双下肢胫前对称性分布紫红色丘疹、斑块,部分斑块上可见水疱,Nikolsky征阴性,局部见散在抓痕、结痂。皮肤病理示表皮下裂隙形成,直接免疫荧光结果IgG,IgA,IgM,C1q,C3a均阴性。确诊为痒疹样营养不良型大疱性表皮松解症。     

Epidermolysis bullosa nevus arising in a patient with Dowling–Meara type epidermolysis bullosa simplex with a novel K5 mutation

We report herein a 4-year-old girl with Dowling–Meara type epidermolysis bullosa (EB) who presented with peculiar pigmented nevi. Blister formation had repeatedly occurred on the erythematous plaques in a circinate fashion since birth, and marked hyperkeratosis was observed on the palms and soles associated with nail deformity. Her mother and maternal grandmother also had similar symptoms. In addition to the blistering lesions, the patient had three large, asymmetrical, pigmented plaques with color variegation. Light and electron microscopic findings of the blistering lesions showed a subepidermal blister with intracytoplasmic granules in keratinocytes as well as degeneration of basal cells and aggregation of tonofilaments. The pigmented lesions revealed histopathological features of compound nevus without malignant changes. Gene analysis revealed an E478K (Glu to Lys) mutation in exon 5 of the keratin 5 ( K5 ) gene. These findings, together with clinical features, were consistent with those of Dowling–Meara type EB associated with so-called EB nevus.