Year: 2021
Type: Article
Title: Genetic Analysis of a Cohort of 275 Patients with Hyper-IgE Syndromes and/or Chronic Mucocutaneous Candidiasis
Author: Frede, Natalie
Author: Rojas-Restrepo, Jessica
Author: Caballero Garcia de Oteyza, Andrés
Author: Buchta, Mary
Author: Hübscher, Katrin
Author: Gámez-Díaz, Laura
Author: Proietti, Michele
Author: Saghafi, Shiva
Author: Chavoshzadeh, Zahra
Author: Soler-Palacin, Pere
Author: Galal, Nermeen
Author: Adeli, Mehdi
Author: Aldave-Becerra, Juan Carlos
Author: Al-Ddafari, Moudjahed Saleh
Author: Ardenyz, Ömür
Author: Atkinson, T Prescott
Author: Kut, Fulya Bektas
Author: Çelmeli, Fatih
Author: Rees, Helen
Author: Kilic, Sara S
Author: Kirovski, Ilija
Author: Klein, Christoph
Author: Kobbe, Robin
Author: Korganow, Anne-Sophie
Author: Lilic, Desa
Author: Lunt, Peter
Author: Makwana, Niten
Author: Metin, Ayse
Author: Özgür, Tuba Turul
Author: Karakas, Ayse Akman
Author: Seneviratne, Suranjith
Author: Sherkat, Roya
Author: Sousa, Ana Berta
Author: Unal, Ekrem
Author: Patiroglu, Turkan
Author: Wahn, Volker
Author: von Bernuth, Horst
Author: Whiteford, Margo
Author: Doffinger, Rainer
Author: Jouhadi, Zineb
Author: Grimbacher, Bodo
Abstract: Hyper-IgE syndromes and chronic mucocutaneous candidiasis constitute rare primary immunodeficiency syndromes with an overlapping clinical phenotype. In recent years, a growing number of underlying genetic defects have been identified. To characterize the underlying genetic defects in a large international cohort of 275 patients, of whom 211 had been clinically diagnosed with hyper-IgE syndrome and 64 with chronic mucocutaneous candidiasis, targeted panel sequencing was performed, relying on Agilent HaloPlex and Illumina MiSeq technologies. The targeted panel sequencing approach allowed us to identify 87 (32 novel and 55 previously described) mutations in 78 patients, which generated a diagnostic success rate of 28.4%. Specifically, mutations in DOCK8 (26 patients), STAT3 (21), STAT1 (15), CARD9 (6), AIRE (3), IL17RA (2), SPINK5 (3), ZNF341 (2), CARMIL2/RLTPR (1), IL12RB1 (1), and WAS (1) have been detected. The most common clinical findings in this cohort were elevated IgE (81.5%), eczema (71.7%), and eosinophilia (62.9%). Regarding infections, 54.7% of patients had a history of radiologically proven pneumonia, and 28.3% have had other serious infections. History of fungal infection was noted in 53% of cases and skin abscesses in 52.9%. Skeletal or dental abnormalities were observed in 46.2% of patients with a characteristic face being the most commonly reported feature (23.1%), followed by retained primary teeth in 18.9% of patients. Targeted panel sequencing provides a cost-effective first-line genetic screening method which allows for the identification of mutations also in patients with atypical clinical presentations and should be routinely implemented in referral centers.
Publisher: Springer Science and Business Media LLC
Relation: Journal of clinical immunology
Identifier: oai:repository.ukim.mk:20.500.12188/14480
Identifier: http://hdl.handle.net/20.500.12188/14480Identifier: 10.1007/s10875-021-01086-4
Identifier: https://link.springer.com/content/pdf/10.1007/s10875-021-01086-4.pdfIdentifier: https://link.springer.com/article/10.1007/s10875-021-01086-4/fulltext.htmlIdentifier: https://link.springer.com/content/pdf/10.1007/s10875-021-01086-4.pdf
