Abstract：
OBJECTIVE: To further elucidate the clinical, immunological and genetic features of chronic mucocutaneous candidiasis (CMC) due to STAT1 GOF mutation in the Chinese population.
METHODS: Clinical data for a proband were collected, and pedigree analyses were performed. Whole-exome sequencing and targeted Sanger sequencing were conducted to explore genetic factors of a Chinese pedigree involving inherited CMC.
RESULTS: An autosomal dominant CMC pedigree was identified, and both the proband and his father had mucocutaneous Candida infections without involvement of other systems. A rare mutation (c.T1175C) in STAT1 was detected in this CMC pedigree. Multiple sequence alignment revealed that the amino acid position of this mutation (p.M392T) is evolutionarily conserved in vertebrate species. Serum IFN-α was elevated in patients harbouring the mutation. A total of 10 publications reporting 26 CMC patients with STAT1 GOF mutations were retrieved by literature review, and the most common mutation found in previously reported Chinese patients is T385M in the DNA-binding domain.
CONCLUSIONS: STAT1 GOF mutation at c.T1175C (p.M392T) may lead to mucocutaneous Candida infections and an increase in serum IFN-α. T385M in the DNA-binding domain is the most common STAT1 GOF mutation found in the Chinese population.
METHODS: Clinical data for a proband were collected, and pedigree analyses were performed. Whole-exome sequencing and targeted Sanger sequencing were conducted to explore genetic factors of a Chinese pedigree involving inherited CMC.
RESULTS: An autosomal dominant CMC pedigree was identified, and both the proband and his father had mucocutaneous Candida infections without involvement of other systems. A rare mutation (c.T1175C) in STAT1 was detected in this CMC pedigree. Multiple sequence alignment revealed that the amino acid position of this mutation (p.M392T) is evolutionarily conserved in vertebrate species. Serum IFN-α was elevated in patients harbouring the mutation. A total of 10 publications reporting 26 CMC patients with STAT1 GOF mutations were retrieved by literature review, and the most common mutation found in previously reported Chinese patients is T385M in the DNA-binding domain.
CONCLUSIONS: STAT1 GOF mutation at c.T1175C (p.M392T) may lead to mucocutaneous Candida infections and an increase in serum IFN-α. T385M in the DNA-binding domain is the most common STAT1 GOF mutation found in the Chinese population.
摘要：
目的：为了进一步阐明临床，慢性粘膜皮肤念珠菌病（CMC）由于STAT1GOF突变在中国人群中的免疫和遗传特征。
方法：收集先证者的临床数据，并进行了谱系分析。进行了全外显子组测序和靶向Sanger测序，以探索涉及遗传CMC的中国家系的遗传因素。
结果：确定了一个常染色体显性遗传CMC谱系，先证者和他的父亲都有粘膜皮肤念珠菌感染，没有其他系统的参与。一种罕见的突变(c.在该CMC谱系中检测到STAT1中的T1175C）。多序列比对显示该突变的氨基酸位置（p。M392T）在脊椎动物物种中在进化上是保守的。携带突变的患者血清IFN-α升高。通过文献综述，共检索了10篇报告26例CMC患者STAT1GOF突变的出版物，在先前报道的中国患者中发现的最常见突变是DNA结合域中的T385M。
结论：c.T1175C时STAT1GOF突变（p。M392T）可能导致粘膜皮肤念珠菌感染和血清IFN-α增加。DNA结合域中的T385M是在中国人群中发现的最常见的STAT1GOF突变。
方法：收集先证者的临床数据，并进行了谱系分析。进行了全外显子组测序和靶向Sanger测序，以探索涉及遗传CMC的中国家系的遗传因素。
结果：确定了一个常染色体显性遗传CMC谱系，先证者和他的父亲都有粘膜皮肤念珠菌感染，没有其他系统的参与。一种罕见的突变(c.在该CMC谱系中检测到STAT1中的T1175C）。多序列比对显示该突变的氨基酸位置（p。M392T）在脊椎动物物种中在进化上是保守的。携带突变的患者血清IFN-α升高。通过文献综述，共检索了10篇报告26例CMC患者STAT1GOF突变的出版物，在先前报道的中国患者中发现的最常见突变是DNA结合域中的T385M。
结论：c.T1175C时STAT1GOF突变（p。M392T）可能导致粘膜皮肤念珠菌感染和血清IFN-α增加。DNA结合域中的T385M是在中国人群中发现的最常见的STAT1GOF突变。
