Huh Hee Jae, Jhun Byung Woo, Choi Sae Rom, Kim Yae Jean, Yun Sun Ae, Nham Eliel, Kong Taehwan, Ki Chang Seok, Koh Won Jung
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yonsei Med J. 2018 Oct;59(8):1004-1007. doi: 10.3349/ymj.2018.59.8.1004.
Bronchiectasis is a chronic disease characterized by airway infection and inflammation, leading to permanent dilation of the bronchi. Evaluation of underlying etiology is important in managing young bronchiectasis patients with recurrent infections caused by unusual pathogens. The signal transducer and activator of transcription 1 (STAT1) protein plays a key role in STAT signaling and immune system regulation. Heterozygotes for gain-of-function (GOF) alleles of the gene usually display autosomal dominant chronic mucocutaneous candidiasis (CMC) and a wide range of clinical features, such as bronchiectasis. Here, we report on a patient with CMC and bronchiectasis with various types of infections who carried a pathogenic variant of the gene. The 24-year-old female presented with recurrent respiratory bacterial and nontuberculous mycobacterial infections complicated by severe bronchiectasis and CMC. Whole-exome sequencing revealed a c.800C>T (p.Ala267Val) heterozygous mutation in the STAT1 gene. Further analysis by Sanger sequencing of from the patient and her parents revealed the patient had a occurrence of the variant. This is the first report of a Korean patient with a GOF pathogenic variant in . Physicians should be aware of the existence of this variant as a genetic factor associated with CMC and bronchiectasis complicated by recurrent infection.
支气管扩张症是一种以气道感染和炎症为特征的慢性疾病，可导致支气管永久性扩张。对于患有由不常见病原体引起的反复感染的年轻支气管扩张症患者，评估潜在病因对于治疗很重要。信号转导和转录激活因子1（STAT1）蛋白在STAT信号传导和免疫系统调节中起关键作用。该基因功能获得性（GOF）等位基因的杂合子通常表现为常染色体显性慢性黏膜皮肤念珠菌病（CMC）以及广泛的临床特征，如支气管扩张症。在此，我们报告一名患有CMC和支气管扩张症且伴有多种类型感染的患者，其携带该基因的一个致病变异。这名24岁女性表现为反复的呼吸道细菌和非结核分枝杆菌感染，并伴有严重的支气管扩张症和CMC。全外显子测序显示STAT1基因存在一个c.800C>T（p.Ala267Val）杂合突变。对该患者及其父母进行Sanger测序进一步分析显示，该患者存在该变异。这是首例关于韩国患者携带该基因GOF致病变异的报告。医生应意识到该变异作为与CMC以及伴有反复感染的支气管扩张症相关的遗传因素的存在。
