中文摘要：

目的了解先天性厚甲症I型（PC—I）及Ⅱ型（PC-Ⅱ）患者家系的基因突变。探讨其基因突变和临床表现的关系。方法扩增外周血基因组DNA中角蛋白16基因的第1—6外显子及K17基因的第1外显子，对PCR产物进行序列分析。结果PC—I家系（家系1）中患者K16基因第127位密码子由CGC突变CCC，导致K16角蛋白lA区的精氨酸由脯氨酸替代（R127P）；PC-Ⅱ家系（家系2）中2例患者K17基因第99位密码子由CTG突变为CCG，导致K17角蛋白1A区的亮氨酸由脯氨酸替代（L99P），而这两个家系中的正常人及与此两家系无关的50例正常人未发现此突变。结论该PC—I家系存在角蛋白16的R127P突变，PC-Ⅱ家系存在角蛋白17的L99P突变。3例厚甲症患者检测到的2个角蛋白突变均由K16及K17发生错义突变，导致其编码的相应氨基酸由脯氨酸替代。此类突变可引发较重的临床表现，即呈现典型PC—I型或PC-Ⅱ型，不会呈现其他较轻的临床亚型。

英文摘要：

Objective To detect the keratin 16 and keratin 17 gene mutations in two chinese pedigrees of pachyonychia congenita type I （PC -Ⅰ）and Ⅱ（ P -Ⅱ） and to explore the relationship between the genetic mutation and the phenotype of PC. Methods The DNA was extracted from the blood samples of 1 patient with PC - I and 2 patients with PC - Ⅱ, unaffected member of the pedi- gree , and 50 unrelated normal persons. PCR was used to amplify the long fragment containing exon 1 to 6 of keratin 16 and the mutation hot spot in the exon 1 of keratin 17 gene. The PCR products were directly sequenced to detect the mutations. Results Sequencing of the PCR products revealed that the codon 127 （ CGC ） was mutated as CCC in the affected member of the pedigree 1, causing the substitution of asparagine by aspartic acid in codon 127 （R127P） located in the 1A domain of keratin 16 gene. In the affected members of the pedigree 2 , the codon 99 （CTC,） was mutated as CCG causing the substitution of asparagine by aspartic acid in codon 99（L99P） located in the 1A domain of keratin 17 gene. No such mutation was found in the unaffected member of the pedigree and the 50 unrelated controls. Conclusion we report two mutations R127P in K16 and L99P in K17 in three cases with PC. we can make the prediction that proline mutations in the helical 1A domain of K16 or k17 are more likely to lead to PC - I or PC - Ⅱ compared with focal non -epidermolytic palmoplantar keratoderma （FNEPPK）and steatocystoma multiplex （SM）.