三个表皮松解性掌跖角化症家系KRT9基因突变的研究

目的 探讨表皮松解性掌跖角化症家系的KRT9基因突变与临床表现的关系。方法 PCR扩增KRT9基因编码氨基酸的7个外显子,对扩增产物进行变性高效液相色谱分析、DNA测序。结果 在所研究的3个EPPK家系中,发现KRT9基因第1外显子第497位核苷酸A缺失并插入GGCT,导致角蛋白9分子第166位酪氨酸缺失并插入色氨酸和亮氨酸,即Y166delinsWL。片段特异性PCR证实了该突变不是一个常见的多态性,而是国际中间纤维突变库(http://www.interfil.org)中未报道过的一种新突变。结论 KRT9基因497delAinsGGCT突变可能是部分中国人EPPK患者发病的遗传基础。

KRT 9 Gene Mutations in Three Chinese Pedigrees with Epidermolytic Palmoplantar Keratoderma

Objective To investigate the keratin 9 gene mutation in epidermolytic palmoplantar keratoderma (EPPK) and its relationship with clinical manifestations. Methods Three Chinese pedigrees with EPPK were studied. Polymerase chain reaction (PCR) was performed to amplify the seven exons encoded by keratin 9. Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific PCR were used to reveal the sequence variation in the PCR products. Results An insertion-deletion mutation in the exon 1 of keratin 9 497delAinsGGCT, was revealed in all 3 EPPK families, resulting in the keratin 9 change from tyrosine166 to tryptophan and leucine (Y166delinsWL). Allele-specific PCR confirmed that the mutation was not a commonly seen polymorphism, but a novel mutation which has not been reported in The Human Intermediate Filament Mutation Database (http://www.interfil.org). Conclusions A new keratin 9 gene mutation, 497delAinsGGCT, is found in these Chinese EPPK pedigrees, which may be the genetic basis of EPPK.