Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα)

Bainter, Wayne; Lougaris, Vassilios; Wallace, Jacqueline G.; Badran, Yousef R.; Hoyos-Bachiloglu, Rodrigo; Peters, Zachary; Wilkie, Hazel; Das, Mrinmoy; Janssen, Erin; Beano, Abdallah; Farhat, Khaoula Ben; Kam, Christy; Bercich, Luisa; Incardona, Paolo; Villanacci, Vincenzo; Bondioni, Maria Pia; Meini, Antonella; Baronio, Manuela; Abarzua, Phammela; Parolini, Silvia; Tabellini, Giovanna; Maio, Stefano; Schmidt, Birgitta; Goldsmith, Jeffrey D.; Murphy, George M.; Holländer, Georg A.; Plebani, Alessandro; Chou, Janet

doi:10.1126/sciimmunol.abf6723

Cited by 13 publications

(32 citation statements)

References 87 publications

(102 reference statements)

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“…Novel gene defects have been found for most categories of IEI, including novel causes of: Combined immunodeficiencies ( LCP2 (SLP76) [ 12 ], PAX1 [ 13 , 14 ], ITPKB [ 15 ]; SASH3 [ 16 , 17 ], MAN2B2 [ 18 ], COPG1 [ 19 ], IKZF2 [ 20 – 23 ], CHUK [ 24 ], IKZF3 [ 25 , 26 ], CRACR2A [ 27 ], CD28 [ 28 ]) (Table 1 ; Supplementary Table 1 ); Combined immunodeficiencies with syndromic features ( MCM10 [ 29 , 30 ], IL6ST [ 31 – 33 ], DIAPH1 [ 34 ]) (Table 2 ; Supplementary Table 1 ); B cell deficiencies, agammaglobulinemia, or hypogammaglobulinemia ( FNIP1 [ 35 , 36 ], SP1I [ 37 ] , PIK3CG [ 38 , 39 ], POU2AF1 [ 40 ], CTNNBL1 [ 41 ], TNSRSF13 [ 42 ]) (Table 3 ; Supplementary Table 1 ); Immune dysregulation ( RHOG [ 43 ], SOCS1 [ 44 – 46 ], PDCD1 [ 47 ], ELF4 [ 48 , 49 ], TET2 [ 50 ], CEBPE [ 51 ], IKZF1 GOF [ 52 ]) (Table 4 ; Supplementary Table 1 ) neutropenia CXCR2 [ 53 ...…”

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

“…There can be clinical overlap between some genes listed here and those listed in Table 7 Total number of mutant genes: 66. New inborn errors of immunity: 8 ( SLP76 [ 12 ], PAX1 [ 13 , 14 ], ITPKB [ 15 ]; SASH3 [ 16 , 17 ], MAN2B2 [ 18 ], COPG1 [ 19 ], IKZF2 [ 20 – 23 ], CHUK [ 24 ]) SCID severe combined immunodeficiency, CID combined immunodeficiency, EBV Epstein-Barr virus, MHC major histocompatibility complex, HPV human papillomavirus, Treg T regulatory cell, XL X-linked inheritance, AR autosomal recessive inheritance, AD autosomal dominant inheritance, LOF loss-of-function, GOF gain-of-function, FTT failure to thrive…”

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

“…Combined immunodeficiencies ( LCP2 (SLP76) [ 12 ], PAX1 [ 13 , 14 ], ITPKB [ 15 ]; SASH3 [ 16 , 17 ], MAN2B2 [ 18 ], COPG1 [ 19 ], IKZF2 [ 20 – 23 ], CHUK [ 24 ], IKZF3 [ 25 , 26 ], CRACR2A [ 27 ], CD28 [ 28 ]) (Table 1 ; Supplementary Table 1 );…”

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

“…Total number of mutant genes: 66. New inborn errors of immunity: 8 ( SLP76 [ 12 ], PAX1 [ 13 , 14 ], ITPKB [ 15 ]; SASH3 [ 16 , 17 ], MAN2B2 [ 18 ], COPG1 [ 19 ], IKZF2 [ 20 – 23 ], CHUK [ 24 ])…”

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

“…PAX1 [13,14], ITPKB [15]; SASH3 [16,17], MAN2B2 [18], COPG1 [19], IKZF2 [20][21][22][23], CHUK [24], IKZF3 [25,26], CRACR2A [27], CD28 [28]) (Table 1; Supplementary Table 1); • Combined immunodeficiencies with syndromic features (MCM10 [29,30], IL6ST [31][32][33], DIAPH1 [34]) (Table 2; Supplementary Table 1); • B cell deficiencies, agammaglobulinemia, or hypogammaglobulinemia (FNIP1 [35,36], SP1I [37], PIK3CG [38,39], POU2AF1 [40], CTNNBL1 [41], TNSRSF13 [42]) (Table 3; Supplementary Table 1); • Immune dysregulation (RHOG [43], SOCS1 [44][45][46],…”

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

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Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

et al. 2022

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We report the updated classification of inborn errors of immunity, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 55 novel monogenic gene defects, and 1 phenocopy due to autoantibodies, that have either been discovered since the previous update (published January 2020) or were characterized earlier but have since been confirmed or expanded in subsequent studies. While variants in additional genes associated with immune diseases have been reported in the literature, this update includes only those that the committee assessed that reached the necessary threshold to represent novel inborn errors of immunity. There are now a total of 485 inborn errors of immunity. These advances in discovering the genetic causes of human immune diseases continue to significantly further our understanding of molecular, cellular, and immunological mechanisms of disease pathogenesis, thereby simultaneously enhancing immunological knowledge and improving patient diagnosis and management. This report is designed to serve as a resource for immunologists and geneticists pursuing the molecular diagnosis of individuals with heritable immunological disorders and for the scientific dissection of cellular and molecular mechanisms underlying monogenic and related human immune diseases.

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Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

See 3 more Smart Citations

Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

et al. 2022

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Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye

Erman,

Aba,

Ipsir

et al. 2024

J Clin Immunol

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Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients’ long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.

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OTULIN Can Improve Spinal Cord Injury by the NF-κB and Wnt/β-Catenin Signaling Pathways

Wang,

Botchway

et al. 2024

Mol Neurobiol

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Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα)

Abstract: A mutation in human IKKα compromises noncanonical NF-κB signaling resulting in primary immunodeficiency associated with autoimmunity.

Cited by 13 publications

References 87 publications

Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye

OTULIN Can Improve Spinal Cord Injury by the NF-κB and Wnt/β-Catenin Signaling Pathways

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