结节性硬化症并发反常性痤疮1例的临床表现及基因变异分析  

Clinical manifestations and genetic variation analysis of one case of tuberous sclerosis complex complicated by acne inversa

作　　者：张帅 邵依 张守民 李振鲁 李建国 王建波 Zhang Shuai;Shao Yi;Zhang Shoumin;Li Zhenlu;Li Jianguo;Wang Jianbo(Department of Dermatology,Henan Provincial People′s Hospital,Zhengzhou University People′s Hospital,Henan University People′s Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院、郑州大学人民医院、河南大学人民医院皮肤科,郑州450003

出　　处：《中华皮肤科杂志》2024年第12期1130-1133,共4页Chinese Journal of Dermatology

基　　金：河南省自然科学基金(202300410386)。

摘　　要：目的报道1例结节性硬化症并发反常性痤疮及其基因变异情况。方法采集结节性硬化症并发反常性痤疮患者及其弟、父母外周血,采用外显子组测序检测患者基因变异情况,Sanger测序验证,确定致病基因。结果患者皮损表现为面部血管纤维瘤、叶状白斑、鲨鱼皮样斑及皮肤多发粉刺、结节、脓肿、瘢痕,伴癫痫、多发肾囊肿,初步诊断为结节性硬化症并发反常性痤疮。基因检测发现,患者TSC2基因存在杂合移码变异c.3506dupC(p.A1169fs)和NCSTN基因存在杂合无义变异c.123T>G(p.Y41X),其弟及母亲NCSTN基因存在杂合无义变异c.123T>G(p.Y41X),其父亲及健康对照均未发现上述变异。在ClinVar、ExAC、1000g数据库的对照人群中未检索到上述变异。结论TSC2基因变异c.3506dupC与NCSTN基因变异c.123T>G可能是该患者特殊临床表现的致病原因,并可能通过mTORC1通路导致反常性痤疮表型加重。Objective To report a case of tuberous sclerosis complex complicated by acne inversa,and to analyze gene variations.Methods Peripheral blood samples were collected from the patient with tuberous sclerosis complex complicated by acne inversa,her younger brother,and her parents.Exome sequencing was performed to detect gene variations in the patient,and Sanger sequencing to confirm the pathogenic gene mutations.Results The patient clinically presented with facial angiofibromas,ash-leaf macules,and shagreen patches,as well as multiple cutaneous comedones,nodules,abscesses,and scars.The paitent also had epilepsy and multiple renal cysts.The initial diagnosis was tuberous sclerosis complex complicated by acne inversa.Genetic testing for the patient revealed a heterozygous frameshift mutation c.3506dupC(p.A1169fs)in the TSC2 gene and a heterozygous nonsense mutation c.123T>G(p.Y41X)in the NCSTN gene.The heterozygous nonsense mutation c.123T>G(p.Y41X)was also identified in the patient′s younger brother and mother,while no above mutations were identified in the patient′s father or 100 unrelated healthy controls.The above mutations were also not retrieved in the ClinVar,ExAC and 1000g databases.Conclusion The mutation c.3506dupC in the TSC2 gene and mutation c.123T>G in the NCSTN gene may be responsible for the unique clinical manifestations in the patient,and potentially exacerbate the phenotype of acne inversa through the mTORC1 pathway.

关 键 词：结节性硬化症 化脓性汗腺炎 TSC2基因 NCSTN基因 mTORC1通路 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]