【作者】 付兰芹；

【导师】 王宝玺；

【作者基本信息】 中国协和医科大学 ， 皮肤性病学， 2007， 硕士

【摘要】 掌跖角皮症(Palmoplantar Keratoderma)是一组以手掌和足跖部位皮肤高度角化为特征的慢性皮肤病。残毁性掌跖角皮症(Mutilanting Palmoplantar Keratoderma，又称Vohwinkel Syndrome，VS)和Olmsted综合征是其中比较少见的两种特殊类型。VS表现为常染色体显性遗传特点，目前其致病基因尚未明确。多位学者根据其不同的临床表现将导致该病的致病基因定位在GJB2基因和Loricrin基因上，在伴有鱼鳞病样的VS患者检测到Loricrin基因发生了变异；而伴有高频性耳聋、听觉丧失的VS患者则检出GJB2基因变异。Olmsted综合征极其罕见，至今所报道的多为散发病例，个别家族性发病的病例显示为常染色体显性遗传，其致病基因未明确。这二种疾病在临床表型上有重叠。为了探讨中国人VS和Olmsted综合征患者是否存在Loricrin基因突变，我们以一个VS患者和一个Olmsted综合征患者及他们家系部分成员作为研究对象，采用PCR和直接测序的方法筛查其基因组DNA的Loricrin基因的全部编码外显子，发现VS家系中患者和不发病的弟弟在Loricrin基因上存在一处插入突变：即EXON2第101～102bp之间插入GGTGGC 6个碱基，经查阅文献和正常人对照研究证实为Loricrin基因新发现的SNP，未检出致病的基因突变。本研究为今后探讨掌跖角皮症这组临床综合症的致病基因和发病机制提供了资料，为该组疾病今后的研究奠定了基础。更多还原

【Abstract】 Vohwinkel Syndrome (VS) is an autosomal dominant skin disease. The clinicalfeatures of VS include palmoplantar keratoderma, constricting bands andstarfish-shaped hyperkeratotic lesions. Olmsted syndrome is another very rarecongenital condition characterized by mutilating palmoplantar keratoderma andperiorificial keratosis. The phenotype of VS may overlap with Olmsted syndrome.Previous studies proved one variant of VS, ichthyotic variant of VS is caused by genemutation of Loricrin. However, gene mutation of VS and Olmsted syndrome have notbeen identified.In this study, we collected genomic DNA of a Vohwinkel Syndrome patient andan Olmsted syndrome patient and some of their family members. The whole coding ofexon 2 of Loricrin gene were amplified by PCR. Direct DNA sequencing wasemployed to detect the gene mutation. Our study revealed a mutation of Loricrin inthe VS patient, which was proved to be a SNP. There was an insertion of GGTGGCbetween No. 101 and No. 102 base pairs in exon 2. No gene mutations of pathologywere detected. This result provided some data for the study of the etiology and themechanism of Palmoplantar Keratoderma in the further studies.更多还原