A GAIN-OF-FUNCTION MUTATION OF STAT1: A NOVEL GENETIC FACTOR CONTRIBUTING TO CHRONIC MUCOCUTANEOUS CANDIDIASIS

作者：Eslami Narges; Tavakol Marzieh; Mesdaghi Mehrnaz; Gharegozlou Mohammad; Casanova Jean Laurent; Puel Anne; Okada Satoshi; Arshi Saba; Bemanian Mohammad Hassan; Fallahpour Morteza; Molatefi Rasool; Seif Farhad; Zoghi Samaneh; Rezaei Nima; Nabavi Mohammad^*

来源：Acta Microbiologica et Immunologica Hungarica, 2017, 64(2): 191-201.

DOI：10.1556/030.64.2017.014

• gain-of-function mutations in STAT1
• chronic mucocutaneous candidiasis

Heterozygous gain-of-GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) have increasingly been identified as a genetic cause of autosomal-dominant (AD) chronic mucocutaneous candidiasis (CMC). In this article, we describe a 33-year-old man who experienced chronic refractory candidiasis, recurrent otitis media, and pneumonia resulting in bronchiectasis, severe oral and esophageal candidiases with strictures associated with hypothyroidism and immune hemolytic anemia. His son also suffered from persistent candidiasis, chronic diarrhea, poor weight gain, and pneumonia that resulted in his demise because of sepsis. The immunological workup showed that an inverse CD4/CD8 ratio and serum immunoglobulins were all within normal ranges. The laboratory data revealed failure in response to Candida lymphocyte transformation test. In addition, by Sanger sequencing method, we found a heterozygous mutation, Thr385Met (T385M), located in the DNA-binding domain of STAT1, which was previously shown to be GOF. These findings illustrate the broad and variable clinical phenotype of heterozygous STAT1 GOF mutations. However, more clinical information and phenotype-genotype studies are required to define the clinical phenotype caused by AD STAT1 GOF.

• 出版日期2017-6