进行性对称性红斑角化症的遗传异质性

The Evidence for Genetic Heterogeneity of Progressive Symmetric Erythrokeratodermia(PSEK)

目的 探讨兜甲蛋白基因 (LOR)在进行性对称性红斑角化症 (PSEK)发病中的作用。方法 收集一个中国人PSEK家系的血样并提取基因组DNA ,用直接测序法对其LOR序列进行测定 ,并利用 10个多态性微卫星标记对包含LOR的 1q2 1区域进行遗传连锁分析 ,以证实测序结果。结果 测序结果显示本家系患者LOR的编码区和剪接区无致病性突变 ,连锁分析也排除了包含LOR的 1q2 1区域与本病存在连锁的可能性。 结论 排除了LOR突变对该PSEK家系的致病作用 ,首次提供了本病存在遗传异质性的直接实验证据 ;

Objective To investigate the causative role of the loricrin gene for PSEK. Methods To obtain the blood samples of affected and unaffected individuals of a China PSEK pedigree and extract genomic DNA, the whole coding region of the loricrin gene was analyzed by direct sequencing. We also performed genotyping and linkage analysis with 10 polymorphic microsatellite markers spanning the loricrin gene at 1q21.Results No disease-causing mutations were detected in the loricrin gene by direct sequencing and linkage analysis revealed significant exclusion of this locus.Conclusion Our study excluds the loricrin gene which could cause PSEK in this family and provides the evidence for genetic heterogeneity of PSEK.