汗孔角化症患者甲羟戊酸途径相关基因突变情况分析  

Analysis of genetic mutations in mevalonate pathway-related genes in patients with porokeratosis

作　　者：孙瑞凤 朱威[2] 连石[2] 陈慧[2] SUN Ruifeng;ZHU Wei;LIAN Shi;CHEN Hui(Department of Dermatology,Haidian District Maternal and Child Health Hospital,Beijing 100080,China)

机构地区：[1]北京市海淀区妇幼保健院皮肤性病科,北京100080 [2]首都医科大学宣武医院皮肤性病科

出　　处：《实用皮肤病学杂志》2025年第1期21-26,共6页Journal of Practical Dermatology

基　　金：北京市自然科学基金资助项目(7163216)。

摘　　要：目的 验证汗孔角化症(PK)的发病与甲羟戊酸途径相关基因[甲羟戊酸激酶(MVK)、磷酸甲羟戊酸激酶(PMVK)、5焦磷酸甲羟戊酸脱羧酶(MVD)、异戊二烯焦磷酸异构酶(FDPS)]突变有关,分析突变基因的致病性。方法 采用回顾性研究的方法,对2015年9月至2021年6月就诊于首都医科大学宣武医院皮肤性病科门诊诊断为PK的患者进行研究,采用双脱氧核苷酸末端终止法测序(Sanger法测序)检测甲羟戊酸途径相关基因。采用MUpro、Polyphen-2、SIFT评分和HOPE蛋白质预测程序对检测到的突变基因进行致病性预测。结果 本研究共纳入19例PK患者,其中11例为散发PK患者,8例为家族性PK患者。6/11的散发PK和7/8的家族性PK患者检测到突变基因。本研究共检测到8个突变基因,MVD (c.746T> C,p.F249S)、MVK (IVS4+1G> A)、FDPS (c.733C> T,p.P245S)、MVD (c.875A> G,p.N292S)、MVK (IVS3+5G> A)、MVD (c.149C> T,p.T50I)、MVD(c.1A> G,p.M1?)、MVD (c.1203A> G,p.X401W),其中MVD (c.746T> C,p.F249S)、MVD (c.875A> G,p.N292S)、MVD (c.1A> G,p.M1?)、MVK (IVS4+1G> A)已被报道与PK的发病有关。应用MUpro、Polyphen-2、SIFT评分和HOPE预测变异导致的蛋白质结构变化,发现突变均有害。结论 PK的发病与甲羟戊酸途径相关基因突变有关。本研究发现了4个新发突变,FDPS(c.733C> T,p.P245S)、MVK(IVS3+5G> A)、MVD (c.149C> T,p.T50I)、MVD (c.1203A> G,p.X401W),丰富了人类PK的遗传学数据库。MUpro、Polyphen-2、SIFT评分和HOPE蛋白质预测程序用于预测突变基因的致病性具有重大价值。Objective To investigate the association between porokeratosis(PK)pathogenesis and mutations in mevalonate pathwayrelated genes(mevalonate kinase MVK,phosphomevalonate kinase PMVK,mevalonate diphosphate decarboxylase MVD,farnesyl diphosphate synthase FDPS)and analyze the pathogenicity of these mutations.Methods A retrospective study was conducted on PK patients diagnosed at the Dermatology Clinic of Xuanwu Hospital,Capital Medical University,between September 2015 and June 2021.Mevalonate pathway-related genes were sequenced using Sanger sequencing(dideoxynucleotide chain termination method).Pathogenicity predictions for detected mutations were performed using MUpro,Polyphen-2,SIFT scoring,and HOPE protein prediction tools.Results A total of 19 PK patients were enrolled,including 11 sporadic cases and 8 familial cases.Mutations were identified in 6/11 sporadic PK and 7/8 familial PK patients.Eight mutated genes were detected:MVD(c.746T>C,p.F249S),MVK(IVS4+1G>A),FDPS(c.733C>T,p.P245S),MVD(c.875A>G,p.N292S),MVK(IVS3+5G>A),MVD(c.149C>T,p.T50I),MVD(c.1A>G,p.M1?),and MVD(c.1203A>G,p.X401W).Among these,MVD(c.746T>C,p.F249S),MVD(c.875A>G,p.N292S),MVD(c.1A>G,p.M1?),and MVK(IVS4+1G>A)have been previously reported to beassociated with PK.MUpro,Polyphen-2,SIFT,and HOPE analysispredicted that all mutations were deleterious,altering proteinstructure.Conclusion PK pathogenesis is linked to mutations inmevalonate pathway-related genes.This study identified four novelmutations:FDPS(c.733C>T,p.P245S),MVK(IVS3+5G>A),MVD(c.149C>T,p.T50I),and MVD(c.1203A>G,p.X401W),enriching the genetic database for human PK.MUpro,Polyphen-2,SIFT scoring,and HOPE are valuable tools for predicting mutation pathogenicity.

关 键 词：汗孔角化症 甲羟戊酸 基因突变 

分 类 号：R758.68[医药卫生—皮肤病学与性病学] R394.112[医药卫生—临床医学]