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. 2024 Aug;72(4):714-726.
doi: 10.1007/s12026-024-09477-6. Epub 2024 Apr 22.

Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants

Ayca Aykut  1 , Asude Durmaz  2 , Neslihan Karaca  3 , Nesrin Gulez  4 , Ferah Genel  4 , Fatih Celmeli  5 , M Tuba Cogurlu  6 , Mediha Akcan  7 , Dilek Cicek  8 , Funda Erol Cipe  9 , Ayca Kiykim  10 , Alisan Yıldıran  11 , Kursad Unluhizarci  12 , Sara Sebnem Kilic  13 , Guzide Aksu  3 , Omur Ardeniz  14 , Necil Kutukculer  3
Affiliations

Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants

Ayca Aykut et al. Immunol Res. 2024 Aug.

Abstract

Human Inborn Errors of Immunity (IEIs) encompass a clinically and genetically heterogeneous group of disorders, ranging from mild cases to severe, life-threatening types. Among these, Primary Immune Regulatory Disorders (PIRDs) constitute a subset of IEIs characterized by diverse clinical phenotypes, prominently featuring severe atopy, autoimmunity, lymphoproliferation, hyperinflammation, autoinflammation, and susceptibility to malignancies. According to the latest report from the International Union of Immunological Societies (IUIS), PIRDs arise from mutations in various genes including LYST, RAB27A, AP3B1, AP3D1, PRF1, UNC13D, STX11, STXBP2, FAAP24, SLC7A7, RASGRP1, CD70, CTPS1, RLTPR, ITK, MAGT1, PRKCD, TNFRSF9, SH2DIA, XIAP, CD27 (TNFRSF7), FAS (TNFRSF6), FASLG (TNFSF6), CASP10, CASP8, FADD, LRBA, STAT3, AIRE, ITCH, ZAP70, TPP2, JAK1, PEPD, FOXP3, IL2RA, CTLA4, BACH2, IL2RB, DEF6, FERMT1, IL10, IL10RA, IL10RB, NFAT5, TGFB1, and RIPK1 genes. We designed a targeted next-generation sequencing (TNGS) workflow using the Ion AmpliSeq™ Primary Immune Deficiency Research Panel to sequence 264 genes associated with IEIs on the Ion S5™ Sequencer. In this study, we report the identification of 38 disease-causing variants, including 16 novel ones, detected in 40 patients across 15 distinct PIRD genes. The application of next-generation sequencing enabled rapid and precise diagnosis of patients with PIRDs.

Keywords: Next-generation sequencing; Novel mutation; PIRD.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
a Segregation analysis of the family and b SNP array analysis of the index
See this image and copyright information in PMC

References

    1. Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010;125(2):S182–94. 10.1016/j.jaci.2009.07.053 - DOI - PubMed
    1. Bousfiha Aziz, Moundir Abderrahmane, Tangye Stuart G, Picard Capucine, Jeddane Leïla, Al-Herz Waleed, Rundles Charlotte C, Franco Jose Luis, Holland Steven M, Klein Christoph, Morio Tomohiro, Oksenhendler Eric, Puel Anne, Puck Jennifer, Seppänen Mikko R J, Somech Raz, Su Helen C, Sullivan Kathleen E, Torgerson Troy R, Meyts Isabelle. The 2022 Update of IUIS phenotypical classification for human inborn errors of immunity. J Clin Immunol. 2022;42(7):1508–20. 10.1007/s10875-022-01352-z - DOI - PubMed
    1. Tangye Stuart G, Al-Herz Waleed, Bousfiha Aziz, Cunningham-Rundles Charlotte, Franco Jose Luis, Holland Steven M, Klein Christoph, Morio Tomohiro, Oksenhendler Eric, Puel Capucine Picard Anne, Puck Jennifer, Seppänen Mikko R J, Somech Raz, Su Helen C, Sullivan Kathleen E, Torgerson Troy R, Meyts Isabelle. Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee. J Clin Immunol. 2022;42(7):1473–507. 10.1007/s10875-022-01289-3. 10.1007/s10875-022-01289-3 - DOI - PMC - PubMed
    1. López-Nevado Marta, González-Granado Luis I, Ruiz-García Raquel, Pleguezuelo Daniel, Cabrera-Marante Oscar, Salmón Nerea, Blanco-Lobo Pilar, Domínguez-Pinilla Nerea, Rodríguez-Pena Rebeca, Sebastián Elena, Cruz-Rojo Jaime, Olbrich Peter, Ruiz-Contreras Jesús, Paz-Artal Estela, Neth Olaf, Allende Luis M. Primary immune regulatory disorders with an autoimmune lymphoproliferative syndrome-like phenotype: immunologic evaluation, early diagnosis and management. Front Immunol. 2021;12:671755. 10.3389/fimmu.2021.671755. (eCollection 2021). 10.3389/fimmu.2021.671755 - DOI - PMC - PubMed
    1. Walter JE, Ayala IA, Milojevic D. Autoimmunity as a continuum in primary immunodeficiency. Curr Opin Pediatr. 2019;31:851–62. 10.1097/MOP.0000000000000833 - DOI - PMC - PubMed

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