Chinese Pedigree of Chronic Mucocutaneous Candidiasis Due to STAT1 Gain-of-Function Mutation: A Case Study and Literature Review

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.