一个掌跖角化牙周病变综合征家系的组织蛋白酶C基因突变分析

Mutational analysis of the cathepsin C gene in a family of Hart nationality with PapiUon-Lefevre syndrome

目的探讨中国汉族掌跖角化牙周病变综合征[又称帕-勒氏综合征（Papillon-Lefevre syndrome，PKS）]的组织蛋白酶C（cathepsin C，CISC）[又称二肽肽酶Ⅰ（dipeptidyl-peptidaseⅠ，DPPⅠ）]基因的突变特点，为该基因的突变在PLS疾病的表型中所起的作用提供科学资料。方法分析临床诊断为PLS的1例患者及其家庭成员的组织蛋白酶C基因的突变，分别提取患者和其父母、妹妹的基因组DNA，应用PCR和DNA直接测序的方法对该家族成员进行组织蛋白酶C基因突变的检测。结果该例PLS患者存在组织蛋白酶C基因的复合型杂合突变，突变为：第1外显子的第116位碱基G缺失（p．V40S），并使随后的第40～50位氨基酸发生了移码改变；第6外显子的C255S杂合突变突变；第7外显子的F314S错义突变和E335E同义突变。这4个突变均为新的突变位点，健康对照组未发现基因突变。结论组织蛋白酶C基因的突变是引起P15临床显型的病因。

Objective To investigate the mutational characteristics of the cathepsin C gene （ CTSC, also known as dipeptidyl-peptidase Ⅰ gene, DPPⅠ） in a family of Han nationality with Papillon-Lefevre syndrome, and to provide the molecular basis for the phenotype. Methods Genomic DNAs were extracted from the proband, his parents and younger sister after informed consent. Polymerase chain reaction and direct DNA sequencing were carried out to screen the mutations of the cathepsin C gene. Results Compound heterozygous mutations of the cathepsin C gene were identified in the patient. The patient carried one frameshift mutation 116delG in exon 1, one hetemzygous mutation C255S in exon 6, one missense mutation F314S and one sense mutation E335E in exon 7. The four changes were novel mutations of/he cathepsin C gene, which had not been reported previously. None of the mutations were detected in normal controis. Conclusion Mutations of the cathepsin C gene are probably responsible for the phenotype of Papillon-Lefevre syndrome in this family.