STAT1功能获得性突变3例临床特点及基因分析

Clinical characteristics and gene analysis in 3 cases of STAT1 gain-of-function

目的探讨3例慢性皮肤黏膜念珠菌病伴有自身免疫性疾病的信号传导与转录激活因子1(signal transducer and activator of transcription 1,STAT1)功能获得性突变(gain-of-function,GOF)的临床特征及基因特点。方法选取就诊阜阳市人民医院儿科的3例确诊为STAT1 GOF的患儿,对其临床特征进行分析总结,采集外周血样,运用高通量测序(high-throughput sequencing,NGS)进行基因检测,并同时进行父母的基因组DNA测序。结果3例患者均出现慢性皮肤黏膜念珠菌病、支气管扩张,并且伴有不同类型的自身免疫性疾病,基因检测证实均存在STAT1基因突变,有不同的突变位点,3个突变均属功能获得性突变,而父母基因均正常,为新发错义变异。结论STAT1 GOF新发突变易导致慢性皮肤黏膜念珠菌病合并自身免疫性疾病,并且在病程的不同时期STAT1基因突变可能伴随不同的自身免疫性疾病的表现,需定期观察,完善相关基因检测有助于早期诊断,避免漏诊及误诊。

Objective To investigate the clinical and genetic characteristics of signal transducer and activator of transcription 1(STAT1)gain-of-function(GOF)mutations in 3 cases of chronic mucocutaneous candidiasis with autoimmune diseases.Methods Clinical characteristics of three patients who were diagnosed with STAT1 GOF in Department of Pediatrics,Fuyang People’s Hospital were selected and analyzed.Peripheral blood samples were collected to detect the genes by high-throughput sequencing(NGS),and the genomic DNA sequencing of their parents was verified at the same time.Results Three children were found to have chronic mucocutaneous candidiasis,bronchiectasis,and accompanied by different types of autoimmune diseases.Gene detection confirmed that STAT1 gene mutation existed in all cases with different mutation sites,and those three mutations are gain-of-function mutations.The parents’genes were normal,and STAT1 GOF was a new missense mutation.Conclusion STAT1 GOF mutations can easily lead to chronic mucocutaneous candidiasis combined with autoimmune diseases,and STAT1 gene mutations may be accompanied by different manifestations of autoimmune diseases in different stages of the disease.Regular observations are required and relevant genetic testing is helpful to early diagnosing and avoiding missed diagnosis and misdiagnosis.