掌跖角化-牙周破坏综合征(一家系)组织蛋白酶C基因突变及功能分析  

Cathepsin C gene Mutations and Functional Analysis of A Chinese Papillon-Lefèvre Syndrome Family.

作　　者：彭海龙 杨媛[1] 秦满[1] PENG Hailong;YANG Yuan;QIN Man(Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China.)

机构地区：[1]北京大学口腔医学院儿童口腔科,北京100081

出　　处：《口腔医学研究》2022年第7期616-621,共6页Journal of Oral Science Research

摘　　要：目的:对一家系中2名掌跖角化-牙周破坏综合征(Papillon-Lefèvre syndrome,PLS)患者及父母进行CTSC基因突变检测,并对突变的组织蛋白酶C进行简要功能分析。方法:(1)针对一个PLS综合征家系,对其进行CTSC基因测序筛查。(2)对研究中发现的CTSC基因突变位点,采用蛋白质结构预测服务器I-TASSER进行组织蛋白酶C蛋白结构预测分析。(3)提取患者及父母外周静脉血中白细胞,测定组织蛋白酶C的活性,并与正常组对比。结果:(1)本家系中2名PLS患者均发现第六、七外显子的c.774 C>G(p.C258W)和c.1033 T>A(p.Y345N)杂合错义突变,其中c.1033 T>A为首次报道。(2)以上两位点突变后蛋白构象与野生型对比,整体结构并未发生明显改变。(3)2名PLS患者的组织蛋白酶C活性较正常对照组平均降低约77%,父亲及母亲的组织蛋白酶C活性降低约23%及63%。结论:本研究中2例PLS患者均存在CTSC基因的复合型杂合子突变,突变位点为c.774 C>G(p.C258W)和c.1033 T>A(p.Y345N),其中c.1033 T>A为新发现的突变位点。该复合型杂合突变并未造成组织蛋白酶C蛋白结构改变,但会造成组织蛋白酶C活性减低。Objective:To investigate the mutational CTSC gene in two Chinese patients with Papillon-Lefèvre syndrome(PLS;OMIM 245000)and analyze the cathepsin C functions.Methods:Genomic DNA was respectively isolated from peripheral blood samples of the patients and their parents.The CTSC gene was extracted and direct sequencing.The protein structure predictive server I-TASSER was used to analyze the change of Cathepsin C structure.Leukocytes were isolated from the patients and their parents's whole blood.Leukocyte cathepsin C activity was measured.Results:A compound heterozygous mutations c.774 C>G and c.1033 T>A in the CTSC was detected in two patients.The c.1033 T>A mutation was a novel substitution.After analysis of cathepsin C protein's structure,compared with wild-type CTSC,the predictive protein's structure after c.774 C>G and c.1033 T>A mutations had no obvious change.Leukocyte cathepsin C activity of the two patients was lower than normal contrasts on an average of about 77%.The cathepsin C activity of their father and mother reduced about 23%and 63%,respectively.Conclusion:In this research,a compound heterozygous mutations(c.774 C>G and c.1033 T>A)of CTSC gene were identified in two patients.The c.1033 T>A mutation is first reported and this kind of compound heterozygous mutation leads to a decrease of cathepsin C activity,but the protein structures have no change.

关 键 词：掌跖角化-牙周破坏综合征 CTSC基因 组织蛋白酶C 基因突变 

分 类 号：R781.4[医药卫生—口腔医学] R596.1[医药卫生—临床医学]