掌跖角化牙周病综合征一例及组织蛋白酶C基因突变检测  

Papillon-Lefvre syndrome： a case report and mutation analysis of the eathepsin C gene

作　　者：李智铭[1] 刘晶晶[1] 竺海刚 张学奇[1] 林孝华[1] 李秉煦[1] 徐云升[1] 

机构地区：[1]温州医科大学附属第一医院皮肤科,325000

出　　处：《中华皮肤科杂志》2015年第11期767-769,共3页Chinese Journal of Dermatology

基　　金：国家自然科学基金（81272987）;浙江省自然科学基金（LY12H11011）;浙江省温州市科技计划项目（Y20140580）

摘　　要：目的 探讨掌跖角化牙周病综合征患者组织蛋白酶C基因（CTSC）突变的特点。 方法 收集1例掌跖角化牙周病综合征患者的临床资料，采集患者及其父母的外周静脉血各2 ml，同时取100例健康人的静脉血2 ml作为对照。以提取的DNA作为模板，用成对的外显子特异性引物对患者的CTSC基因的全部7个外显子进行PCR扩增后直接测序，检测患者CTSC基因的突变情况。 结果 患者的CTSC基因存在复合型杂合突变，外显子6内第824位碱基C被T置换（c.824C 〉 T），此突变导致CTSC基因第275位氨基酸密码子由ACC替换为ATC，其编码的氨基酸由苏氨酸替换为异亮氨酸（p.T275I）；外显子7内第1040位碱基A被G置换（c.1040A ＞ G），导致CTSC基因第347位氨基酸密码子由TAT替换为TGT，其编码的氨基酸由酪氨酸变为半胱氨酸（p.Y347C）。其中c.824C 〉 T突变是CTSC基因的新突变位点。患者父亲和母亲分别为c.824C 〉 T和c.1040A ＞ G杂合突变。100例健康对照中未发现CTSC基因c.824C 〉 T和c.1040A ＞ G突变。 结论 CTSC基因突变是导致掌跖角化牙周病综合征临床表型的致病原因，c.824C 〉 T突变扩大了CTSC基因的突变谱，为掌跖角化牙周病综合征的基因诊断提供了依据。Objective To analyze mutations in the cathepsin C （CTSC） gene in a patient with Papillon-Lefèvre syndrome （PLS）. Methods Clinical data were collected from a patient with PLS. Two milliliters of venous blood samples were obtained from the patient, his parents and 100 unrelated healthy controls separately. DNA was extracted from these blood samples, and PCR was performed to amplify all the 7 exons of the CTSC gene followed by direct DNA sequencing. Results Two heterozygous mutations were observed in the CTSC gene of the patient. One was a novel mutation c.824C 〉 T at position 824 in the exon 6, which resulted in a substitution of ACC （threonine） by ATC （isoleucine） at codon 275 （p.T275I）. The other one was the mutation c.1040A 〉 G at position 1040 in the exon 7, causing the substitution of TAT （tyrosine） by TGT （cysteine） at codon 347 （p.Y347C）. His father and mother carried the heterozygous mutation c.824C 〉 T and c.1040A 〉 G respectively. Neither of the two mutations was observed in the 100 healthy controls. Conclusions CTSC mutations are responsible for the clinical phenotype of PLS. Identification of the c.824C 〉 T mutation extends the spectrum of mutations in the CTSC gene and provides a basis for genetic diagnosis of PLS.

关 键 词：突变 组织蛋白酶C基因 掌跖角化牙周病综合征 

分 类 号：R758.5[医药卫生—皮肤病学与性病学] R781.4[医药卫生—临床医学]