全外显子组测序鉴定一家系长岛型掌跖角化症SERPINB7基因突变分析黄闰娣王笑宇刘成李荣华余佳林李常兴【摘要】目的对一例临床诊断遗传性掌跖角化症患者进行全外显子组测序分析致病基因。方法收集一例临床诊断遗传性掌跖角化症的临床资料，采集患者及家系成员样本提取外周血DNA，通过全外显子组测序结果筛选致病变异，进一步用Sanger测序进行家系验证。结果一家系成员3人，患者1人，女，17岁，表现为掌跖角化症17年。患者检测到SERPINB7纯合突变c.796C>T（p.Arg266Ter）位点，该突变导致SERPINB7基因編码的蛋白第266位氨基酸由精氨酸变为终止密码。先证者父亲和母亲均检测到SERPINB7杂合突变c.796C>T（p.Arg266Ter）位点。该例患者诊断为长岛型掌跖角化症（Nagashima-typepalmoplantarkeratosis，NPPK）。结论NPPK患者符合常染色体隐性遗传模式，SERPINB7c.796C>T（p.Arg266Ter）基因纯合突变是导致该例NPPK患者的临床表型。【关键词】长岛型掌跖角化症;丝氨酸蛋白酶抑制剂B7;基因;突变：R758.5+3文献标志码：ADOI：10.3969/j.issn.1003-1383.2021.04.004AnalysisonSERPINB7genemutationinafamilywithNagashima-typepalmoplantarkeratosisidentifiedbywholeexomesequencing[HJ2][HJ]HUANGRundi1，WANGXiaoyu2，LIUCheng2，LIRonghua3，YUJialin1，LIChangxing4（1.DepartmentofDermatology，DalangHospitalofDongguan，Dongguan523770，Guangdong，China;2.DepartmentofDermatology，GuangdongArmedPoliceCorpsGeneralHospitalAffiliatedtoGuangzhouMedicalUniversity，Guangzhou510517，Guangdong，China;3.DepartmentofDermatology，QuanzhouFirstHospitalAffiliatedtoFujianMedicalUniversity，Quanzhou362000，Fujian，China;4.DepartmentofDermatology，NanfangHospitalofSouthernMedicalUniversity，Guangzhou510515，Guangdong，China）[HJ2][HJ]【Abstract】ObjectiveTocarryoutwholeexomesequencingon1caseofhereditarypalmoplantarkeratosisdiagnosedintheclinic，soastoanalyzepathogenicgenesofit.MethodsTheclinicaldataofacaseofhereditarypalmoplantarkeratosiswerecollected.ThesamplesofthepatientandherfamilymemberswerecollectedtoextracttheperipheralbloodDNA.Pathogenicvariantswerescreenedbytheresultsofwholeexomesequencing，andSangersequencingwasusedforfurtherfamilyverification.ResultsThefamily（3members）includeda17-year-oldfemalepatient，characterizedbypalmoplantarkeratosisfor17years.AhomozygousmutationofSERPINB7c.796C>T（p.Arg266Ter）wasidentifiedinthepatient，whichcausedtheprotein266aminoacidencodedbytheSERPINB7genetochangefromargininetoterminationcode.SERPINB7heterozygousmutationc.796C>T（p.Arg266Ter）locuswasdetectedinbothfatherandmotherofthepatient.SothepatientwasdiagnosedwithNagashima-typepalmoplantarkeratosis（NPPK）.ConclusionTheNPPKpatientisconsistentwithautosomalrecessiveinheritancepattern，andSERPINB7c.796C>T（p.Arg266Ter）homozygousmutationisresponsiblefortheclinicalphenotypeofthisNPPKpatient.【Keywords】NPPK;SERPINB7;gene;mutation长岛型掌跖角化症（Nagashima-typepalmoplantarkeratosis，NPPK）首先在日本报告，是一种罕见的先天性掌跖角化症，遗传模式符合常染色体隐性遗传，临床表现为掌跖等部位出现红斑、丘疹、斑块、角化，常伴真菌感染或手足多汗症[1～2]。课题组前期的研究显示NPPK的致病基因为丝氨酸蛋白酶抑制剂B7（SERPINB7）[2～4]。本課题组前期收集一例临床诊断为先天性掌跖角化症患者，通过全外显子组测序和Sanger测序发现患者及其母亲检测到SERPINB7基因8号外显子存在突变，现将结果报道如下。1资料与方法1.1病例资料患者女，17岁，因“掌跖部位皮疹17年”就诊。患者出生后不久掌跖部位出现红斑，随年龄的增长，掌跖部位皮肤增长，出现斑块、角化、脱屑，无痒无痛。在当地医院按“湿疹、手足癣”等治疗，疗效不佳。皮肤科专科检查：双手掌、掌背、手腕...