The design of specific next generation sequencing panels has allowed to diagnose patients with a specific phenotype a timely and cost-efficient manner. Chronic mucocutaneous candidiasis (CMC) has been described as part of the spectrum of patients with primary immunodeficiencies (PID). Here we report our experience with a specific gene panel applied to paediatric and adult patients with CMC in our setting.
NGS was performed using an AmpliSeq strategy on an Ion Torrent PGM platform. The panel included six genes related to CMC (STAT1, TRAF3IP2, CARD9, IL17F, IL17RA e IL17RC).
Eleven patients were included in this study and one paediatric patient was found to have a compound heterozygous mutation in TRAF3IP2. This patient is a 6 year old girl born to non-consanguineous healthy parents. CMC appeared in the first year of life and has been controlled since then with intermittent treatment with fluconazole. She did not suffer from any other infections or autoimmune diseases.
The mutations have not been previously reported. Whilst one is a nucleotide deletion (c.1335delA) resulting in a stop codon (p.Lys445fs*11) the second mutation (c.1325A>G) leads which a different amino acid (Asp442Gly) and is, following the used theoretic algorithms, pathogenic. The patient showed increased IL17 levels after stimulation with PMA and Ionomycin.
By using a specifically designed NGS panel we were able to identify a patient with ACT1 deficiency an extremely rare PID. Although further functional testing, the presence of CMC suggests the pathogenic effect of these mutations