表皮松解性角化过度型鱼鳞病二例及其基因突变的研究

Gene Mutations in Two Sporadic Cases of Epidermolytic Hyperkeratosis Ichthyosis

目的研究二例表皮松解性角化过度型鱼鳞病患者基因突变情况。方法取患者皮损进行组织病理及电镜检查;提取患者外周血DNA,采用聚合酶链反应及DNA直接测序方法,检测患者皮损角蛋白10(K10)及角蛋白1(K1)基因突变;等位基因特异性引物PCR及限制性内切酶片段长度多态性方法筛查正常人群中该等位基因频率。结果2例患者均存在K1或K10基因的杂合点突变,即K10基因第2140位G→A,K1基因第4226位G→A,分别导致K10第156位的精氨酸变为组氨酸(R156H)及K1第477位氨基酸从谷氨酸变为赖氨酸(E477K),而正常对照无此替代。结论K10R156H及K1E477K为导致这2例患者临床表型的特异突变。

Objective To identify gene mutations of two cases of epidermolytic hyperkeratosis ichthyosis.Methods Punch biopsies were taken from typical lesions for histopathological examination by light microscopy and transmission electron microscopy.Genomic DNA was extracted from blood samples.Mutations of keratin1(K1)and keratin10(K10)were detected by polymerase chain reaction(PCR)and DNA sequencing;Frequencies of the alleles were screened by PCR-based allele-specific assays(PASA)and restriction fragment-length polymorphism(RFLP)in normal controls.Results There was a single heterozygous point mutation in either K1or K10genes,i.e.2140G→A of K10gene and4226G→A of K1gene,leading to an amino acid alteration of arginine to histidine(K10R156H)and glutamic acid to lysine(K1E477K),respectively.These substitutions were not found in normal controls.Conclusion K10R156H and K1E477K mutations were the cause of the phenotypes in these two cases.