先天性厚甲症2型一家系的基因突变研究

Gene mutation of pachyonychia congenita Ⅱ:A family case analysis

目的研究先天性厚甲症的基因突变,从而探讨基因型与表现型之间的关系。方法提取1个先天性厚甲症家系中先证者及其家人的外周血基因组DNA,用聚合酶链反应扩增,产物测序检测。取先证者母亲的皮损做组织病理检查,观察皮损组织的角蛋白17的表达。结果家系中两患者的角蛋白17的1号外显子第275位碱基发生A→G的杂合突变,其突变导致其编码角蛋白17的第92位氨基酸的密码子发生改变,使其编码的氨基酸由天冬酰胺变为丝氨酸(N92S)。先证者母亲皮损组织病理检查为多发性脂囊瘤,免疫组化显示角蛋白17阳性表达。结论验证了角蛋白17的1号外显子α螺旋1A区突变在先天性厚甲症发病机制中的重要作用。角蛋白17 1A区突变对脂囊瘤的早发可能存在一定影响,基因型与表型存在一定关联。

Objective To explore the relationship between the genotype and the clinical phenotypes through investigating gene mutation in pachyonychia congenital （PC）. Methods Genomic DNA of the proband and her family members （including the affected and normal） with blood relationship were extracted with a peripheral blood genomic DNA extraction kit, and using polymerase chain reaction （PCR）-mediated amplification of I exon of keratin 17 gene. Direct sequencing of all PCR products was performed to detect the mutation. Skin biopsy was taken from the proband＇s mother of PC processed for histopathologic examination eosinophilic staining of the hematoxylin, and immunohistochemistry staining to observe the expression of keratin 27. Results （X） PCR amplification products were sequenced. Results disclosed a heterozygous A to G transition at nucleotide position 275 of exon 1＇ of keratin 17 in the affected members of PC. This nucleotide substitution caused change of codon 92 from asparagine into serine （N92S） in the 1A domain of keratin 17. （2） The results of skin biopsy of the proband＇ s mother showed steatocystoma multiplex and immunohistochemical staining showed positive expression of keratin 17. Conclusion Our study validated the important role of keratin 17 1A domain mutation in the pathogenesis of PC, Keratin 17 1A domain mutation seems to have a certain influence on the early occurrence of steatocystoma, There is a correlation between genotype and phenotype of Keratin 17 1A domain mutation.