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

doi:10.13701/j.cnki.kqyxyj.2022.07.007

口腔医学研究 ›› 2022, Vol. 38 ›› Issue (7): 616-621.DOI: 10.13701/j.cnki.kqyxyj.2022.07.007

• 儿童口腔发育性疾病研究 • 上一篇下一篇

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

彭海龙, 杨媛^*, 秦满

北京大学口腔医学院儿童口腔科北京 100081

收稿日期:2022-01-19 出版日期:2022-07-28 发布日期:2022-07-22
通讯作者: * 杨媛,E-mail:phloong@126.com
作者简介:彭海龙(1989~ ),男,北京人,医师,博士,研究方向:掌趾掌跖角化-牙周破坏综合征分子生物学研究。

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

PENG Hailong, YANG Yuan^*, QIN Man

Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China

Received:2022-01-19 Online:2022-07-28 Published:2022-07-22

摘要/Abstract

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。

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

Abstract: 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.

Key words: Papillon-Lefèvre syndrome, CTSC gene, cathepsin C, gene mutation

彭海龙, 杨媛, 秦满. 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[J]. 口腔医学研究, 2022, 38(7): 616-621.

PENG Hailong, YANG Yuan, QIN Man. Cathepsin C gene Mutations and Functional Analysis of A Chinese Papillon-Lefèvre Syndrome Family[J]. Journal of Oral Science Research, 2022, 38(7): 616-621.

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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

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