【作者】 崔勇；

【导师】 杨森； 张学军；

【作者基本信息】 安徽医科大学 ， 皮肤性病学， 2003， 硕士

【摘要】 进行性对称性红斑角化症的临床表型分析及突变筛查 红斑角化症是一组以广泛分布的红斑(固定或移动)为特征，伴随掌跖角化等表现的疾病，主要有两种临床亚型：可变性红斑角化症(EKV)和进行性对称性红斑角化症(PSEK)，二者均为具有不完全外显率和差异表达的常染色体显性遗传性皮肤病，但其分子发病机制目前仍不清楚。目前仅Ishida-Yamamoto等对PSEK等进行了系列研究，但其研究结果受到了其他学者的怀疑；国内尚无关于PSEK的临床表型及分子遗传学的系统研究。本研究旨在探讨中国人群中PESK的临床表型特点及其一致和差异性，并对其家系传递特点进行分析，同时采用测序的方法筛查某些候选致病基因的突变，以期为明确其分子发病机制提供新的线索。 本研究检索并收集国内自1980年以来报道的6个PSEK家系资料，分析和比较了不同家系间临床表型和传递模式，同时参考OMIM记载的分子遗传学信息选择了几个候选致病基因，并对其中一个家系中患者的这些基因进行了突变筛查。 对6个PSEK家系的临床表型及遗传资料进行比较分析结果显示：1)多数患者早年发病，表型至青春期发展充分；2)典型皮损为对称分布的散在红色斑块，表面出现角化和鳞屑，部分患者可出现特殊表型；3)本病在家系中的传递基本均呈连续性，成员发病无显著性别差异，同胞中患者比例接近1／2；4)患者群体中绝大部分临床表型充分表现，但外显率并非100％。 对其中一个PSEK家系进行的候选致病基因突变筛查结果显示：1)Loricin基因未发生突变；2)EKV相关致病基因GJB3和GJB4也未见突变发生。 本研究结果表明：1)中国人PSEK的临床表型谱及遗传特点与其他人群无显著差异；2)本病外显率高，但不同患者临床表型之间存在差异表达；3)本病存在遗传异质性，很可能存在其他致病基因，值得进一步进行研究。更多还原

【Abstract】 The term erythrokeratoderma (EK) means a heterogeneous group of disorders characterized by the mixture of erythematous and hyperkeratotic lesions by dissimilar mode; two major clinical subtypes have been described as erymrokeratodermia variabilis and progressive symmetric erythrokeratodermia. Both of them are autosomal dominant diseases with incomplete penetrance and variable expression and their molecular mechanism are unknown. Ishida-Yamamoto have acomplished serial study on PSEK, but his results had received suspicion from other researchers. To explore the penotype features, inheritance mode and molecular mechanism of PSEK patients in China, we analyzed the clinical features of 6 Chinese PSEK pedigrees which have been published since 1980 and performed mutation detection in some candidate genes by direct sequencing.The results about penotype shows: (1)most patients occurs during the first year or childhood, and the illness state fully develops in adulthood; (2)the typical lesion is hyperkeratotic erythematous with small scales, and some patients have distinguishing penotypes; (3)the disease transfer continuously in pedigrees, patients have no difference in gender and disease affect about half member in brethren; (4)clinical penotypes of most patients fully express but penetrance is not 100%.The results of mutation detection show there are no mutations on Loricrin gene and candidate genes of EKV (GJB3 and GJB4) .We concluded: (1)the penotype spectrum and inheritance feature of Chinese PSEK are similar with other ethnic group; (2)PSEK in Chinese group also shows high penetrance and variable expressivity; (3)the genetic mechanism of PSEK may exist mutation heterogeneity, or there are other genes take part in its pathogenesis, and more investigation are needed in discovery of the molecular mechanism of PSEK.更多还原