先天性大疱性鱼鳞病样红皮病基因突变检测

Mutation analysis of KRTIO gene in a patient with bullous congenital ichthyosiform erythroderma

目的研究1例先天性大疱性鱼鳞病样红皮病散发患者的基因突变情况，探讨基因型与表现型的相关性。方法应用聚合酶链反应扩增KRT1和KRT10基因的热点突变区，通过DNA直接测序的方法，对先天性大疱性鱼鳞病样红皮病患者、家系中的正常成员和50名无亲缘关系的正常个体的KRT1和KRT10基因进行突变检测。结果在患者KRT10基因的第1外显子上发现了1个错义突变（467G→A），导致角蛋白10（KRT10）1A区的精氨酸由组氨酸替代（R156H），而家系正常成员和无亲缘关系的50名正常对照中均未发现该突变。结论KRT10基因第1外显子突变（467G→A）在该例先天性大疱性鱼鳞病样红皮病患病的分子机制中发挥重要作用。

Objective To investigate the gene mutation in one sporadic case of bullous congenital ichthyosiform erythroderma （BCIE）, and to explore the relationship between the genotype and phenotype. Methods DNA was extracted from the blood samples of the patient with BCIE, unaffected members of the pedigree, and 50 unrelated healthy controls. PCR was used to amplify the hot spot fragment of keratin 1 （KRT1） and keratin 10 （KRTIO）gene. The PCR products were directly sequenced to detect the mutations. Results A heterozygous 467G→A mutation was found in the patient, resulting in the substitution of arginine （R） by histidine （PI） in eodon 156 （R156H） in the 1A domain of the KRT10 protein but not in the healthy individuals from the family and the 50 unrelated individuals. Conclusion The mutation of 467G→A in exon 1 of KRT10 gene identified may play a major role in the pathogenic mechanism of this case of BCIE.