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Cited by 279Immunodeficiency and Autoimmune DisordersT-cell and B-cell ImmunologyBlood disorders and treatments

Genes associated with common variable immunodeficiency: one diagnosis to rule them all?

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Bogaert, Delfien J A, Dullaers, Melissa, Lambrecht, Bart N, Vermaelen, Karim Y, De Baere, Elfride, Haerynck, Filomeen·2016·Journal of Medical Genetics
DOI 10.1136/jmedgenet-2015-103690
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Abstract

Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by hypogammaglobulinaemia, impaired production of specific antibodies after immunisation and increased susceptibility to infections. CVID shows a considerable phenotypical and genetic heterogeneity. In contrast to many other primary immunodeficiencies, monogenic forms count for only 2–10% of patients with CVID. Genes that have been implicated in monogenic CVID include ICOS, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), TNFRSF7 (CD27), IL21, IL21R, LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R1, VAV1, RAC2, BLK, IKZF1 (IKAROS) and IRF2BP2. With the increasing number of disease genes identified in CVID, it has become clear that CVID is an umbrella diagnosis and that many of these genetic defects cause distinct disease entities. Moreover, there is accumulating evidence that at least a subgroup of patients with CVID has a complex rather than a monogenic inheritance. This review aims to discuss current knowledge regarding the molecular genetic basis of CVID with an emphasis on the relationship with the clinical and immunological phenotype.

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  • CVID is genetically diverse, with 2% of published cases estimated to be due to mutations in the PLCG2 gene.

    “PLAID is specifically driven by a gain-of-function amino acid mutation in the PLCγ2 gene (63, 64), whereas CVID is much more genetically diverse with 2% of published cases of CVID estimated to be due to mutations in the PLCG2 gene (65).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [65]

    The Introduction and ‘Complex forms of CVID’ sections describe CVID as genetically diverse and say that monogenic causes have been identified in 2–10% of patients. The PLCγ2 section reports that some patients with PLCG2-related PLAID met CVID diagnostic criteria, but it does not estimate that PLCG2 mutations account for 2% of published CVID cases. Page numbers are unavailable in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • A significant gain of function of PLCγ2 can lead to deleterious impacts on the immune system.

    “These clearly indicate that a significant gain of function of PLCγ2 can lead to deleterious impacts on the immune system.”

    From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [35]

  • PLCγ2 is implicated in immunodeficiency including PLAID and CVID.

    “Given its prominent role in the adaptive immune system, PLCγ2 has been implicated in manifestations of immunodeficiency, including both the immunodeficiency syndrome, PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) and common variable immunodeficiency (CVID).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [65]

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Research works printed but not linked: 124

  1. Modell V, Quinn J, Orange J, Notarangelo LD, Modell F. Primary immunodeficiencies worldwide: an updated overview from the Jeffrey Modell Centers Global Network. Immunol Res 2016;64:736-53.
  2. Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, Espinosa-Rosales FJ, Hammarström L, Nonoyama S, Quinti I, Routes JM, Tang ML, Warnatz K. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract 2016;4:38-59.
  3. Tseng CW, Lai KL, Chen DY, Lin CH, Chen HH. The incidence and prevalence of common variable immunodeficiency disease in Taiwan, a population-based study. PLoS ONE 2015;10:e0140473.
  4. van Schouwenburg PA, Davenport EE, Kienzler AK, Marwah I, Wright B, Lucas M, Malinauskas T, Martin HC, Lockstone HE, Cazier JB, Chapel HM, Knight JC, Patel SY. Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders. Clin Immunol 2015;160:301-14.
  5. Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Dräger R, Eibel H, Fischer B, Schäffer AA, Mages HW, Kroczek RA, Peter HH. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol 2003;4:261-8.
  6. Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet 2005;37:829-34.
  7. Salzer U, Chapel HM, Webster AD, Pan-Hammarström Q, Schmitt-Graeff A, Schlesier M, Peter HH, Rockstroh JK, Schneider P, Schäffer AA, Hammarström L, Grimbacher B. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet 2005;37:820-8.
  8. Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Böhm J, Kienzler AK, Pan-Hammarström Q, Hammarström L, Rakhmanov M, Schlesier M, Grimbacher B, Peter HH, Eibel H. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci USA 2009;106:13945-50.
  9. Li J, Jørgensen SF, Maggadottir SM, Bakay M, Warnatz K, Glessner J, Pandey R, Salzer U, Schmidt RE, Perez E, Resnick E, Goldacker S, Buchta M, Witte T, Padyukov L, Videm V, Folseraas T, Atschekzei F, Elder JT, Nair RP, Winkelmann J, Gieger C, Nöthen MM, Büning C, Brand S, Sullivan KE, Orange JS, Fevang B, Schreiber S, Lieb W, Aukrust P, Chapel H, Cunningham-Rundles C, Franke A, Karlsen TH, Grimbacher B, Hakonarson H, Hammarstrom L, Ellinghaus E. Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells. Nat Commun 2015;6:6804.
  10. Salzer U, Maul-Pavicic A, Cunningham-Rundles C, Urschel S, Belohradsky BH, Litzman J, Holm A, Franco JL, Plebani A, Hammarstrom L, Skrabl A, Schwinger W, Grimbacher B. ICOS deficiency in patients with common variable immunodeficiency. Clin Immunol 2004;113:234-40.
  11. Takahashi N, Matsumoto K, Saito H, Nanki T, Miyasaka N, Kobata T, Azuma M, Lee SK, Mizutani S, Morio T. Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. J Immunol 2009;182:5515-27.
  12. Chou J, Massaad MJ, Cangemi B, Bainter W, Platt C, Badran YR, Raphael BP, Kamin DS, Goldsmith JD, Pai SY, Al-Herz W, Geha RS. A novel mutation in ICOS presenting as hypogammaglobulinemia with susceptibility to opportunistic pathogens. J Allergy Clin Immunol 2015;136:794-97.e1.
  13. Robertson N, Engelhardt KR, Morgan NV, Barge D, Cant AJ, Hughes SM, Abinun M, Xu Y, Koref MS, Arkwright PD, Hambleton S. Astute clinician report: a novel 10 bp frameshift deletion in exon 2 of ICOS causes a combined immunodeficiency associated with an enteritis and hepatitis. J Clin Immunol 2015;35:598-603.
  14. Warnatz K, Bossaller L, Salzer U, Skrabl-Baumgartner A, Schwinger W, van der Burg M, van Dongen JJ, Orlowska-Volk M, Knoth R, Durandy A, Draeger R, Schlesier M, Peter HH, Grimbacher B. Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency. Blood 2006;107:3045-52.
  15. Mudter J, Wirtz S, Weigmann B, Tiede I, Tubbe I, Kiesslich R, Galle PR, Lehr HA, Neurath MF. Crohn's-like colitis in a patient with immunodeficiency associated with a defect in expression of inducible costimulator. Dig Dis Sci 2006;51:711-7.
  16. Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 2011;244:115-33.
  17. Zhang Y, Li J, Zhang YM, Zhang XM, Tao J. Effect of TACI signaling on humoral immunity and autoimmune diseases. J Immunol Res 2015;2015:247426.
  18. Castigli E, Wilson S, Garibyan L, Rachid R, Bonilla F, Schneider L, Morra M, Curran J, Geha R. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet 2007;39:430-1.
  19. Pan-Hammarström Q, Salzer U, Du L, Björkander J, Cunningham-Rundles C, Nelson DL, Bacchelli C, Gaspar HB, Offer S, Behrens TW, Grimbacher B, Hammarström L. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet 2007;39:429-30.
  20. Salzer U, Bacchelli C, Buckridge S, Pan-Hammarström Q, Jennings S, Lougaris V, Bergbreiter A, Hagena T, Birmelin J, Plebani A, Webster AD, Peter HH, Suez D, Chapel H, McLean-Tooke A, Spickett GP, Anover-Sombke S, Ochs HD, Urschel S, Belohradsky BH, Ugrinovic S, Kumararatne DS, Lawrence TC, Holm AM, Franco JL, Schulze I, Schneider P, Gertz EM, Schäffer AA, Hammarström L, Thrasher AJ, Gaspar HB, Grimbacher B. Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes. Blood 2009;113:1967-76.
  21. Martinez-Gallo M, Radigan L, Almejún MB, Martínez-Pomar N, Matamoros N, Cunningham-Rundles C. TACI mutations and impaired B-cell function in subjects with CVID and healthy heterozygotes. J Allergy Clin Immunol 2013;131:468-76.
  22. Pieper K, Rizzi M, Speletas M, Smulski CR, Sic H, Kraus H, Salzer U, Fiala GJ, Schamel WW, Lougaris V, Plebani A, Hammarstrom L, Recher M, Germenis AE, Grimbacher B, Warnatz K, Rolink AG, Schneider P, Notarangelo LD, Eibel H. A common single nucleotide polymorphism impairs B-cell activating factor receptor's multimerization, contributing to common variable immunodeficiency. J Allergy Clin Immunol 2014;133:1222-25.e10.
  23. Lougaris V, Gallizzi R, Vitali M, Baronio M, Salpietro A, Bergbreiter A, Salzer U, Badolato R, Plebani A. A novel compound heterozygous TACI mutation in an autosomal recessive common variable immunodeficiency (CVID) family. Hum Immunol 2012;73:836-9.
  24. Martinez-Pomar N, Detková D, Arostegui JI, Alvarez A, Soler-Palacin P, Vidaller A, Espanol T, Sampalo A, de Gracia J, Hernandez M, Yagüe J, Matamoros N. Role of TNFRSF13B variants in patients with common variable immunodeficiency. Blood 2009;114:2846-8.
  25. Kutukculer N, Gulez N, Karaca NE, Aksu G, Berdeli A. Three different classifications, B lymphocyte subpopulations, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) gene mutations, CTLA-4 and ICOS gene polymorphisms in Turkish patients with common variable immunodeficiency. J Clin Immunol 2012;32:1165-79.
  26. Mohammadi J, Liu C, Aghamohammadi A, Bergbreiter A, Du L, Lu J, Rezaei N, Amirzargar AA, Moin M, Salzer U, Pan-Hammarström Q, Hammarström L. Novel mutations in TACI (TNFRSF13B) causing common variable immunodeficiency. J Clin Immunol 2009;29:777-85.
  27. Speletas M, Mamara A, Papadopoulou-Alataki E, Iordanakis G, Liadaki K, Bardaka F, Kanariou M, Germenis AE. TNFRSF13B/TACI alterations in Greek patients with antibody deficiencies. J Clin Immunol 2011;31:550-9.
  28. Almejun MB, Cols M, Zelazko M, Oleastro M, Cerutti A, Oppezzo P, Cunningham-Rundles C, Danielian S. Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination. Eur J Immunol 2013;43:805-14.
  29. Sathkumara HD, De Silva NR, Handunnetti S, De Silva AD. Genetics of common variable immunodeficiency: role of transmembrane activator and calcium modulator and cyclophilin ligand interactor. Int J Immunogenet 2015;42:239-53.
  30. Romberg N, Chamberlain N, Saadoun D, Gentile M, Kinnunen T, Ng YS, Virdee M, Menard L, Cantaert T, Morbach H, Rachid R, Martinez-Pomar N, Matamoros N, Geha R, Grimbacher B, Cerutti A, Cunningham-Rundles C, Meffre E. CVID-associated TACI mutations affect autoreactive B cell selection and activation. J Clin Invest 2013;123:4283-93.
  31. Losi CG, Silini A, Fiorini C, Soresina A, Meini A, Ferrari S, Notarangelo LD, Lougaris V, Plebani A. Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients with common variable immunodeficiency. J Clin Immunol 2005;25:496-502.
  32. Kienzler AK, Salzer U, Warnatz K, Grimbacher B, Rolink A, Pan-Hammarstrom Q, Hammarstrom L, Peter HH, Eibel H. Human BAFF-R deficiency is associated with primary antibody deficiency syndrome. Clin Immunol 2009;131:S123-S23.
  33. Ochtrop ML, Goldacker S, May AM, Rizzi M, Draeger R, Hauschke D, Stehfest C, Warnatz K, Goebel H, Technau-Ihling K, Werner M, Salzer U, Eibel H, Schlesier M, Peter HH. T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency. Blood 2011;118:309-18.
  34. Germinaro M, Reynolds P, Knight V, Alam R. Association of B-cell activating factor receptor deficiency with the P21R polymorphism and common variable immunodeficiency. Ann Allergy Asthma Immunol 2015;115:82-3.
  35. Lougaris V, Baronio M, Moratto D, Cardinale F, Plebani A. Monoallelic BAFFR P21R/H159Y Mutations and Familiar Primary Antibody Deficiencies. J Clin Immunol 2016;36:1-3.
  36. Hildebrand JM, Luo Z, Manske MK, Price-Troska T, Ziesmer SC, Lin W, Hostager BS, Slager SL, Witzig TE, Ansell SM, Cerhan JR, Bishop GA, Novak AJ. A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling. J Exp Med 2010;207:2569-79.
  37. Wang HY, Ma CA, Zhao Y, Fan X, Zhou Q, Edmonds P, Uzel G, Oliveira JB, Orange J, Jain A. Antibody deficiency associated with an inherited autosomal dominant mutation in TWEAK. Proc Natl Acad Sci USA 2013;110:5127-32.
  38. van Zelm MC, Reisli I, van der Burg M, Castano D, van Noesel CJ, van Tol MJ, Woellner C, Grimbacher B, Patino PJ, van Dongen JJ, Franco JL. An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med 2006;354:1901-12.
  39. van Zelm MC, Smet J, Adams B, Mascart F, Schandené L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest 2010;120:1265-74.
  40. Thiel J, Kimmig L, Salzer U, Grudzien M, Lebrecht D, Hagena T, Draeger R, Volxen N, Bergbreiter A, Jennings S, Gutenberger S, Aichem A, Illges H, Hannan JP, Kienzler AK, Rizzi M, Eibel H, Peter HH, Warnatz K, Grimbacher B, Rump JA, Schlesier M. Genetic CD21 deficiency is associated with hypogammaglobulinemia. J Allergy Clin Immunol 2012;129:801-10.e6.
  41. Kanegane H, Agematsu K, Futatani T, Sira MM, Suga K, Sekiguchi T, van Zelm MC, Miyawaki T. Novel mutations in a Japanese patient with CD19 deficiency. Genes Immun 2007;8:663-70.
  42. Conley ME, Dobbs AK, Farmer DM, Kilic S, Paris K, Grigoriadou S, Coustan-Smith E, Howard V, Campana D. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol 2009;27:199-227.
  43. Artac H, Reisli I, Kara R, Pico-Knijnenburg I, Adin-Çinar S, Pekcan S, Jol-van der Zijde CM, van Tol MJ, Bakker-Jonges LE, van Dongen JJ, van der Burg M, van Zelm MC. B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele. Genes Immun 2010;11:523-30.
  44. van Zelm MC, Smet J, van der Burg M, Ferster A, Le PQ, Schandené L, van Dongen JJ, Mascart F. Antibody deficiency due to a missense mutation in CD19 demonstrates the importance of the conserved tryptophan 41 in immunoglobulin superfamily domain formation. Hum Mol Genet 2011;20:1854-63.
  45. Vince N, Boutboul D, Mouillot G, Just N, Peralta M, Casanova JL, Conley ME, Bories JC, Oksenhendler E, Malphettes M, Fieschi C. Defects in the CD19 complex predispose to glomerulonephritis, as well as IgG1 subclass deficiency. J Allergy Clin Immunol 2011;127:538-41.e1-5.
  46. Skendros P, Rondeau S, Chateil JF, Bui S, Bocly V, Moreau JF, Theodorou I, Aladjidi N. Misdiagnosed CD19 deficiency leads to severe lung disease. Pediatr Allergy Immunol 2014;25:603-6.
  47. Vences-Catalán F, Kuo CC, Sagi Y, Chen H, Kela-Madar N, van Zelm MC, van Dongen JJ, Levy S. A mutation in the human tetraspanin CD81 gene is expressed as a truncated protein but does not enable CD19 maturation and cell surface expression. J Clin Immunol 2015;35:254-63.
  48. van Zelm MC, Bartol SJ, Driessen GJ, Mascart F, Reisli I, Franco JL, Wolska-Kusnierz B, Kanegane H, Boon L, van Dongen JJ, van der Burg M. Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation. J Allergy Clin Immunol 2014;134:135-44.
  49. Wentink MW, Lambeck AJ, van Zelm MC, Simons E, van Dongen JJ, JIspeert H, Schölvinck EH, van der Burg M. CD21 and CD19 deficiency: two defects in the same complex leading to different disease modalities. Clin Immunol 2015;161:120-7.
  50. Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IA, Dolman KM, Beaumont T, Tedder TF, van Noesel CJ, Eldering E, van Lier RA. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest 2010;120:214-22.
  51. van Montfrans JM, Hoepelman AI, Otto S, van Gijn M, van de Corput L, de Weger RA, Monaco-Shawver L, Banerjee PP, Sanders EA, Jol-van der Zijde CM, Betts MR, Orange JS, Bloem AC, Tesselaar K. CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J Allergy Clin Immunol 2012;129:787-93 e6.
  52. Alkhairy OK, Perez-Becker R, Driessen GJ, Abolhassani H, van Montfrans J, Borte S, Choo S, Wang N, Tesselaar K, Fang M, Bienemann K, Boztug K, Daneva A, Mechinaud F, Wiesel T, Becker C, Dückers G, Siepermann K, van Zelm MC, Rezaei N, van der Burg M, Aghamohammadi A, Seidel MG, Niehues T, Hammarström L. Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency. J Allergy Clin Immunol 2015;136:703-12.e10.
  53. Salzer E, Daschkey S, Choo S, Gombert M, Santos-Valente E, Ginzel S, Schwendinger M, Haas OA, Fritsch G, Pickl WF, Förster-Waldl E, Borkhardt A, Boztug K, Bienemann K, Seidel MG. Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. Haematologica 2013;98:473-8.
  54. Kotlarz D, Ziętara N, Milner JD, Klein C. Human IL-21 and IL-21R deficiencies: two novel entities of primary immunodeficiency. Curr Opin Pediatr 2014;26:704-12.
  55. Salzer E, Kansu A, Sic H, Májek P, Ikincioğullari A, Dogu FE, Prengemann NK, Santos-Valente E, Pickl WF, Bilic I, Ban SA, Kuloğlu Z, Demir AM, Ensari A, Colinge J, Rizzi M, Eibel H, Boztug K. Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. J Allergy Clin Immunol 2014;133:1651-9.e12.
  56. Kotlarz D, Ziętara N, Uzel G, Weidemann T, Braun CJ, Diestelhorst J, Krawitz PM, Robinson PN, Hecht J, Puchałka J, Gertz EM, Schäffer AA, Lawrence MG, Kardava L, Pfeifer D, Baumann U, Pfister ED, Hanson EP, Schambach A, Jacobs R, Kreipe H, Moir S, Milner JD, Schwille P, Mundlos S, Klein C. Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome. J Exp Med 2013;210:433-43.
  57. Stepensky P, Keller B, Abuzaitoun O, Shaag A, Yaacov B, Unger S, Seidl M, Rizzi M, Weintraub M, Elpeleg O, Warnatz K. Extending the clinical and immunological phenotype of human interleukin-21 receptor deficiency. Haematologica 2015;100: e72-6.
  58. Erman B, Bilic I, Hirschmugl T, Salzer E, Çagdas D, Esenboga S, Akcoren Z, Sanal O, Tezcan I, Boztug K. Combined immunodeficiency with CD4 lymphopenia and sclerosing cholangitis caused by a novel loss-of-function mutation affecting IL21R. Haematologica 2015;100:e216-9.
  59. Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM, Phadwal K, Simon AK, Moutschen M, Etzioni A, Mory A, Srugo I, Melamed D, Hultenby K, Liu C, Baronio M, Vitali M, Philippet P, Dideberg V, Aghamohammadi A, Rezaei N, Enright V, Du L, Salzer U, Eibel H, Pfeifer D, Veelken H, Stauss H, Lougaris V, Plebani A, Gertz EM, Schaffer AA, Hammarström L, Grimbacher B. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet 2012;90:986-1001.
  60. Kuehn HS, Ouyang W, Lo B, Deenick EK, Niemela JE, Avery DT, Schickel JN, Tran DQ, Stoddard J, Zhang Y, Frucht DM, Dumitriu B, Scheinberg P, Folio LR, Frein CA, Price S, Koh C, Heller T, Seroogy CM, Huttenlocher A, Rao VK, Su HC, Kleiner D, Notarangelo LD, Rampertaap Y, Olivier KN, McElwee J, Hughes J, Pittaluga S, Oliveira JB, Meffre E, Fleisher TA, Holland SM, Lenardo MJ, Tangye SG, Uzel G. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 2014;345:1623-7.
  61. Schubert D, Bode C, Kenefeck R, Hou TZ, Wing JB, Kennedy A, Bulashevska A, Petersen BS, Schäffer AA, Grüning BA, Unger S, Frede N, Baumann U, Witte T, Schmidt RE, Dueckers G, Niehues T, Seneviratne S, Kanariou M, Speckmann C, Ehl S, Rensing-Ehl A, Warnatz K, Rakhmanov M, Thimme R, Hasselblatt P, Emmerich F, Cathomen T, Backofen R, Fisch P, Seidl M, May A, Schmitt-Graeff A, Ikemizu S, Salzer U, Franke A, Sakaguchi S, Walker LS, Sansom DM, Grimbacher B. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med 2014;20:1410-6.
  62. Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, Zhang Y, Liu Z, Fritz JM, Marsh R, Husami A, Kissell D, Nortman S, Chaturvedi V, Haines H, Young LR, Mo J, Filipovich AH, Bleesing JJ, Mustillo P, Stephens M, Rueda CM, Chougnet CA, Hoebe K, McElwee J, Hughes JD, Karakoc-Aydiner E, Matthews HF, Price S, Su HC, Rao VK, Lenardo MJ, Jordan MB. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 2015;349:436-40.
  63. Alangari A, Alsultan A, Adly N, Massaad MJ, Kiani IS, Aljebreen A, Raddaoui E, Almomen AK, Al-Muhsen S, Geha RS, Alkuraya FS. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol 2012;130:481-8.e2.
  64. Burns SO, Zenner HL, Plagnol V, Curtis J, Mok K, Eisenhut M, Kumararatne D, Doffinger R, Thrasher A, Nejentsev S. LRBA gene deletion in a patient presenting with autoimmunity without hypogammaglobulinemia. J Allergy Clin Immunol 2012;130:1428-32.
  65. Charbonnier LM, Janssen E, Chou J, Ohsumi TK, Keles S, Hsu JT, Massaad MJ, Garcia-Lloret M, Hanna-Wakim R, Dbaibo G, Alangari AA, Alsultan A, Al-Zahrani D, Geha RS, Chatila TA. Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like disorder caused by loss-of-function mutations in LRBA. J Allergy Clin Immunol 2015;135:217-27.
  66. Revel-Vilk S, Fischer U, Keller B, Nabhani S, Gámez-Diaz L, Rensing-Ehl A, Gombert M, Hönscheid A, Saleh H, Shaag A, Borkhardt A, Grimbacher B, Warnatz K, Elpeleg O, Stepensky P. Autoimmune lymphoproliferative syndrome-like disease in patients with LRBA mutation. Clin Immunol 2015;159:84-92.
  67. Seidel MG, Hirschmugl T, Gamez-Diaz L, Schwinger W, Serwas N, Deutschmann A, Gorkiewicz G, Zenz W, Windpassinger C, Grimbacher B, Urban C, Boztug K. Long-term remission after allogeneic hematopoietic stem cell transplantation in LPS-responsive beige-like anchor (LRBA) deficiency. J Allergy Clin Immunol 2015;135:1384-90.e1-8.
  68. Serwas NK, Kansu A, Santos-Valente E, Kuloğlu Z, Demir A, Yaman A, Yaneth Gamez Diaz L, Artan R, Sayar E, Ensari A, Grimbacher B, Boztug K. Atypical manifestation of LRBA deficiency with predominant IBD-like phenotype. Inflamm Bowel Dis 2015;21:40-7.
  69. Gámez-Diaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG, Noriko M, Morio T, Worth AJ, Blessing J, Van de Veerdonk F, Feuchtinger T, Kanariou M, Schmitt-Graeff A, Jung S, Seneviratne S, Burns S, Belohradsky BH, Rezaei N, Bakhtiar S, Speckmann C, Jordan M, Grimbacher B. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol 2016;137:223-30.
  70. Sari S, Dogu F, Hwa V, Haskologlu S, Dauber A, Rosenfeld R, Polat M, Kuloglu Z, Kansu A, Dalgic B, Ikinciogullari A. A successful HSCT in a girl with novel LRBA mutation with refractory celiac disease. J Clin Immunol 2016;36:8-11.
  71. Alkhairy OK, Abolhassani H, Rezaei N, Fang M, Andersen KK, Chavoshzadeh Z, Mohammadzadeh I, El-Rajab MA, Massaad M, Chou J, Aghamohammadi A, Geha RS, Hammarström L. Spectrum of Phenotypes Associated with Mutations in LRBA. J Clin Immunol 2016;36:33-45.
  72. Schreiner F, Plamper M, Dueker G, Schoenberger S, Gámez-Díaz L, Grimbacher B, Hilger AC, Gohlke B, Reutter H, Woelfle J. Infancy-onset T1DM, short stature, and severe immunodysregulation in two siblings with a homozygous LRBA mutation. J Clin Endocrinol Metab 2016;101:898-904.
  73. Hayakawa S, Okada S, Tsumura M, Sakata S, Ueno Y, Imai K, Morio T, Ohara O, Chayama K, Kobayashi M. A Patient with CTLA-4 Haploinsufficiency Presenting Gastric Cancer. J Clin Immunol 2016;36:28-32.
  74. Zeissig S, Petersen BS, Tomczak M, Melum E, Huc-Claustre E, Dougan SK, Laerdahl JK, Stade B, Forster M, Schreiber S, Weir D, Leichtner AM, Franke A, Blumberg RS. Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4. Gut 2015;64:1889-97.
  75. Salzer E, Santos-Valente E, Klaver S, Ban SA, Emminger W, Prengemann NK, Garncarz W, Müllauer L, Kain R, Boztug H, Heitger A, Arbeiter K, Eitelberger F, Seidel MG, Holter W, Pollak A, Pickl WF, Förster-Waldl E, Boztug K. B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C delta. Blood 2013;121:3112-6.
  76. Angulo I, Vadas O, Garçon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C, Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J, Kracker S, Debré M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G, Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A, Nejentsev S. Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science 2013;342:866-71.
  77. Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK, Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA, Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL, Lenardo MJ, Uzel G. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nat Immunol 2014;15:88-97.
  78. Kuehn HS, Boisson B, Cunningham-Rundles C, Reichenbach J, Stray-Pedersen A, Gelfand EW, Maffucci P, Pierce KR, Abbott JK, Voelkerding KV, South ST, Augustine NH, Bush JS, Dolen WK, Wray BB, Itan Y, Cobat A, Sorte HS, Ganesan S, Prader S, Martins TB, Lawrence MG, Orange JS, Calvo KR, Niemela JE, Casanova JL, Fleisher TA, Hill HR, Kumanovics A, Conley ME, Rosenzweig SD. Loss of B Cells in Patients with Heterozygous Mutations in IKAROS. N Engl J Med 2016;374:1032-43.
  79. Keller MD, Pandey R, Li D, Glessner J, Tian L, Henrickson SE, Chinn IK, Monaco-Shawver L, Heimall J, Hou C, Otieno FG, Jyonouchi S, Calabrese L, van Montfrans J, Orange JS, Hakonarson H. Mutation in IRF2BP2 is responsible for a familial form of common variable immunodeficiency disorder. J Allergy Clin Immunol Published Online First: 23 Mar 2016. doi:10.1016/j.jaci.2016.01.018 · DOI
  80. Belot A, Kasher PR, Trotter EW, Foray AP, Debaud AL, Rice GI, Szynkiewicz M, Zabot MT, Rouvet I, Bhaskar SS, Daly SB, Dickerson JE, Mayer J, O'Sullivan J, Juillard L, Urquhart JE, Fawdar S, Marusiak AA, Stephenson N, Waszkowycz B, W Beresford M, Biesecker LG, C MBlack G, René C, Eliaou JF, Fabien N, Ranchin B, Cochat P, Gaffney PM, Rozenberg F, Lebon P, Malcus C, Crow YJ, Brognard J, Bonnefoy N. Protein kinase cδ deficiency causes Mendelian systemic lupus erythematosus with B cell-defective apoptosis and hyperproliferation. Arthritis Rheum 2013;65:2161-71.
  81. Kuehn HS, Niemela JE, Rangel-Santos A, Zhang M, Pittaluga S, Stoddard JL, Hussey AA, Evbuomwan MO, Priel DA, Kuhns DB, Park CL, Fleisher TA, Uzel G, Oliveira JB. Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans. Blood 2013;121:3117-25.
  82. Kiykim A, Ogulur I, Baris S, Salzer E, Karakoc-Aydiner E, Ozen AO, Garncarz W, Hirschmugl T, Krolo A, Yucelten AD, Boztug K, Barlan IB. Potentially beneficial effect of hydroxychloroquine in a patient with a novel mutation in protein kinase Cδ deficiency. J Clin Immunol 2015;35:523-6.
  83. Ombrello MJ, Remmers EF, Sun G, Freeman AF, Datta S, Torabi-Parizi P, Subramanian N, Bunney TD, Baxendale RW, Martins MS, Romberg N, Komarow H, Aksentijevich I, Kim HS, Ho J, Cruse G, Jung MY, Gilfillan AM, Metcalfe DD, Nelson C, O'Brien M, Wisch L, Stone K, Douek DC, Gandhi C, Wanderer AA, Lee H, Nelson SF, Shianna KV, Cirulli ET, Goldstein DB, Long EO, Moir S, Meffre E, Holland SM, Kastner DL, Katan M, Hoffman HM, Milner JD. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med 2012;366:330-8.
  84. Zhou Q, Lee GS, Brady J, Datta S, Katan M, Sheikh A, Martins MS, Bunney TD, Santich BH, Moir S, Kuhns DB, Long Priel DA, Ombrello A, Stone D, Ombrello MJ, Khan J, Milner JD, Kastner DL, Aksentijevich I. A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. Am J Hum Genet 2012;91:713-20.
  85. Chen K, Coonrod EM, Kumánovics A, Franks ZF, Durtschi JD, Margraf RL, Wu W, Heikal NM, Augustine NH, Ridge PG, Hill HR, Jorde LB, Weyrich AS, Zimmerman GA, Gundlapalli AV, Bohnsack JF, Voelkerding KV. Germline mutations in NFKB2 implicate the noncanonical NF-κB pathway in the pathogenesis of common variable immunodeficiency. Am J Hum Genet 2013;93:812-24.
  86. Fliegauf M, V LB, Frede N, Slade C, Woon ST, Lehnert K, Winzer S, Bulashevska A, Scerri T, Leung E, Jordan A, Keller B, de Vries E, Cao H, Yang F, Schaffer AA, Warnatz K, Browett P, Douglass J, Ameratunga RV, van der Meer JW, Grimbacher B. Haploinsufficiency of the NF-κB1 subunit p50 in common variable immunodeficiency. Am J Hum Genet 2015;97:389-403.
  87. Brue T, Quentien MH, Khetchoumian K, Bensa M, Capo-Chichi JM, Delemer B, Balsalobre A, Nassif C, Papadimitriou DT, Pagnier A, Hasselmann C, Patry L, Schwartzentruber J, Souchon PF, Takayasu S, Enjalbert A, Van Vliet G, Majewski J, Drouin J, Samuels ME. Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies. BMC Med Genet 2014;15:139.
  88. Lee CE, Fulcher DA, Whittle B, Chand R, Fewings N, Field M, Andrews D, Goodnow CC, Cook MC. Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood 2014;124:2964-72.
  89. Lindsley AW, Qian Y, Valencia CA, Shah K, Zhang K, Assa'ad A. Combined immune deficiency in a patient with a novel NFKB2 mutation. J Clin Immunol 2014;34:910-5.
  90. Liu Y, Hanson S, Gurugama P, Jones A, Clark B, Ibrahim MA. Novel NFKB2 Mutation in Early-Onset CVID. J Clin Immunol 2014;34:686-90.
  91. Lougaris V, Tabellini G, Vitali M, Baronio M, Patrizi O, Tampella G, Biasini A, Moratto D, Parolini S, Plebani A. Defective natural killer-cell cytotoxic activity in NFKB2-mutated CVID-like disease. J Allergy Clin Immunol 2015;135:1641-3.
  92. Jou ST, Chien YH, Yang YH, Wang TC, Shyur SD, Chou CC, Chang ML, Lin DT, Lin KH, Chiang BL. Identification of variations in the human phosphoinositide 3-kinase p110delta gene in children with primary B-cell immunodeficiency of unknown aetiology. Int J Immunogenet 2006;33:361-9.
  93. Crank MC, Grossman JK, Moir S, Pittaluga S, Buckner CM, Kardava L, Agharahimi A, Meuwissen H, Stoddard J, Niemela J, Kuehn H, Rosenzweig SD. Mutations in PIK3CD can cause hyper IgM syndrome (HIGM) associated with increased cancer susceptibility. J Clin Immunol 2014;34:272-6.
  94. Hartman HN, Niemela J, Hintermeyer MK, Garofalo M, Stoddard J, Verbsky JW, Rosenzweig SD, Routes JM. Gain of function mutations of PIK3CD as a cause of primary sclerosing cholangitis. J Clin Immunol 2015;35:11-4.
  95. Kracker S, Curtis J, Ibrahim MAA, Sediva A, Salisbury J, Campr V, Debré M, Edgar JDM, Imai K, Picard C, Casanova JL, Fischer A, Nejentsev S, Durandy A. Occurrence of B-cell lymphomas in patients with activated phosphoinositide 3-kinase δ syndrome. J Allergy Clin Immunol 2014;134:233-6.
  96. Chiriaco M, Brigida I, Ariganello P, Di Cesare S, Di Matteo G, Taus F, Cittaro D, Lazarevic D, Scarselli A, Santilli V, Attardi E, Stupka E, Giannelli S, Fraziano M, Finocchi A, Rossi P, Aiuti A, Palma P, Cancrini C. A case of APDS patient: defects in maturation and function and decreased in vitro anti-mycobacterial activity in the myeloid compartment. Clin Immunol Published Online First: 27 Dec 2015. doi:10.1016/j.clim.2015.12.008 · DOI
  97. Elgizouli M, Lowe DM, Speckmann C, Schubert D, Hulsdunker J, Eskandarian Z, Dudek A, Schmitt-Graeff A, Wanders J, Jorgensen SF, Fevang B, Salzer U, Nieters A, Burns S, Grimbacher B. Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency. Clin Exp Immunol 2016;183:221-9.
  98. Deau MC, Heurtier L, Frange P, Suarez F, Bole-Feysot C, Nitschke P, Cavazzana M, Picard C, Durandy A, Fischer A, Kracker S. A human immunodeficiency caused by mutations in the PIK3R1 gene. J Clin Invest 2014;124:3923-8.
  99. Lucas CL, Zhang Y, Venida A, Wang Y, Hughes J, McElwee J, Butrick M, Matthews H, Price S, Biancalana M, Wang X, Richards M, Pozos T, Barlan I, Ozen A, Rao VK, Su HC, Lenardo MJ. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. J Exp Med 2014;211:2537-47. 100
  100. Parry DA, Maisuria S, Argumugacani G, Logan CV, Wood PM, Cant A, Gooi HC, Johnson CA, Nejentsev S, Doody G, Savic S. Mutation of Phosphoinositide-3-Kinase Regulatory Subunit Alpha 1, Leading to Hyperactivation of Phosphoinositide-3-Kinase, Results in an Immunodeficiency Resembling APDS. J Clin Immunol 2014;34:S179. 101
  101. Kuhlen M, Hönscheid A, Loizou L, Nabhani S, Fischer U, Stepensky P, Schaper J, Klapper W, Siepermann M, Schuster F, Meisel R, Borkhardt A. De novo PIK3R1 gain-of-function with recurrent sinopulmonary infections, long-lasting chronic CMV-lymphadenitis and microcephaly. Clin Immunol 2016;162:27-30. 102
  102. Conley ME, Dobbs AK, Quintana AM, Bosompem A, Wang YD, Coustan-Smith E, Smith AM, Perez EE, Murray PJ. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. J Exp Med 2012;209:463-70. 103
  103. Capitani N, Ariani F, Amedei A, Pezzicoli A, Matucci A, Vultaggio A, Troilo A, Renieri A, Baldari CT, D'Elios MM. Vav1 haploinsufficiency in a common variable immunodeficiency patient with defective T-cell function. Int J Immunopathol 2012;25:811-7. 104
  104. Alkhairy OK, Rezaei N, Graham RR, Abolhassani H, Borte S, Hultenby K, Wu C, Aghamohammadi A, Williams DA, Behrens TW, Hammarström L, Pan-Hammarström Q. RAC2 loss-of-function mutation in 2 siblings with characteristics of common variable immunodeficiency. J Allergy Clin Immunol 2015;135:1380-4. e1-5. 105
  105. Compeer EB, Janssen W, van Royen-Kerkhof A, van Gijn M, van Montfrans JM, Boes M. Dysfunctional BLK in common variable immunodeficiency perturbs B-cell proliferation and ability to elicit antigen-specific CD4+ T-cell help. Oncotarget 2015;6:10759-71. 106
  106. Bousfiha A, Jeddane L, Al-Herz W, Ailal F, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Franco JL, Gaspar HB, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Picard C, Puck JM, Sullivan KE, Tang ML. The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies. J Allergy Clin Immunol 2015;35:727-38. 107
  107. Chou J, Lutskiy M, Tsitsikov E, Notarangelo LD, Geha RS, Dioun A. Presence of hypogammaglobulinemia and abnormal antibody responses in GATA2 deficiency. J Allergy Clin Immunol 2014;134:223-6. 108
  108. Buchbinder D, Baker R, Lee YN, Ravell J, Zhang Y, McElwee J, Nugent D, Coonrod EM, Durtschi JD, Augustine NH, Voelkerding KV, Csomos K, Rosen L, Browne S, Walter JE, Notarangelo LD, Hill HR, Kumánovics A. Identification of patients with RAG mutations previously diagnosed with common variable immunodeficiency disorders. J Clin Immunol 2015;35:119-24. 109
  109. Abolhassani H, Wang N, Aghamohammadi A, Rezaei N, Lee YN, Frugoni F, Notarangelo LD, Pan-Hammarström Q, Hammarström L. A hypomorphic recombination-activating gene 1 (RAG1) mutation resulting in a phenotype resembling common variable immunodeficiency. J Allergy Clin Immunol 2014;134:1375-80. 110
  110. Abolhassani H, Cheraghi T, Rezaei N, Aghamohammadi A, Hammarstrom L. Common variable immunodeficiency or late-onset combined immunodeficiency: a new hypomorphic JAK3 patient and review of the literature. J Investig Allergol Clin Immunol 2015;25:218-20. 111
  111. Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Björkman A, Schäffer AA, Fliegauf M, Sayar EH, Salzer U, Fisch P, Pfeifer D, Di Virgilio M, Cao H, Yang F, Zimmermann K, Keles S, Caliskaner Z, Güner SÜ, Schindler D, Hammarström L, Rizzi M, Hummel M, Pan-Hammarström Q, Schwarz K, Grimbacher B. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. Hum Mol Genet 2015;24:7361-72. 112
  112. De Leeneer K, Hellemans J, Steyaert W, Lefever S, Vereecke I, Debals E, Crombez B, Baetens M, Van Heetvelde M, Coppieters F, Vandesompele J, De Jaegher A, De Baere E, Coucke P, Claes K. Flexible, scalable, and efficient targeted resequencing on a benchtop sequencer for variant detection in clinical practice. Hum Mutat 2015;36:379-87. 113
  113. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013;369:1502-11. 114
  114. Meienberg J, Bruggmann R, Oexle K, Matyas G. Clinical sequencing: is WGS the better WES? Hum Genet 2016;135:359-62. 115
  115. Di Pierro V, Zuntini R, Cancrini C, Finocchi A, Angelino G, Rossi P, Ferrari S. Consanguinity and polygenic diseases: a model for antibody deficiencies. Hum Hered 2014;77:144-9. 116
  116. Orange JS, Glessner JT, Resnick E, Sullivan KE, Lucas M, Ferry B, Kim CE, Hou C, Wang F, Chiavacci R, Kugathasan S, Sleasman JW, Baldassano R, Perez EE, Chapel H, Cunningham-Rundles C, Hakonarson H. Genome-wide association identifies diverse causes of common variable immunodeficiency. J Allergy Clin Immunol 2011;127:1360-7.e6. 117
  117. Rodríguez-Cortez VC, Del Pino-Molina L, Rodríguez-Ubreva J, Ciudad L, Gómez-Cabrero D, Company C, Urquiza JM, Tegnér J, Rodríguez-Gallego C, López-Granados E, Ballestar E. Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naive-to-memory B-cell transition. Nat Commun 2015;6:7335. 118
  118. Offer SM, Pan-Hammarström Q, Hammarström L, Harris RS. Unique DNA repair gene variations and potential associations with the primary antibody deficiency syndromes IgAD and CVID. PLoS ONE 2010;5:e12260. 119
  119. Flinsenberg TW, Janssen WJ, Herczenik E, Boross P, Nederend M, Jongeneel LH, Scholman RC, Boelens JJ, Maas C, van Gijn ME, van Montfrans JM, Leusen JH, Boes M. A novel FcγRIIa Q27W gene variant is associated with common variable immune deficiency through defective FcγRIIa downstream signaling. Clin Immunol 2014;155:108-17. 120
  120. Packwood K, Drewe E, Staples E, Webster D, Witte T, Litzman J, Egner W, Sargur R, Sewell W, Lopez-Granados E, Seneviratne SL, Powell RJ, Ferry BL, Chapel HM. NOD2 polymorphisms in clinical phenotypes of common variable immunodeficiency disorders. Clin Exp Immunol 2010;161:536-41. 121
  121. Bellacchio E, Palma A, Corrente S, Di Girolamo F, Helen Kemp E, Di Matteo G, Comelli L, Carsetti R, Cascioli S, Cancrini C, Fierabracci A. The possible implication of the S250C variant of the autoimmune regulator protein in a patient with autoimmunity and immunodeficiency: in silico analysis suggests a molecular pathogenic mechanism for the variant. Gene 2014;549:286-94. 122
  122. Borte S, Celiksoy MH, Menzel V, Ozkaya O, Ozen FZ, Hammarström L, Yildiran A. Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency. Clin Immunol 2014;154:105-11. 123
  123. Vorechovský I, Cullen M, Carrington M, Hammarström L, Webster AD. Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families. J Immunol 2000;164:4408-16. 124
  124. Liao M, Ye F, Zhang B, Huang L, Xiao Q, Qin M, Mo L, Tan A, Gao Y, Lu Z, Wu C, Zhang Y, Zhang H, Qin X, Hu Y, Yang X, Mo Z. Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese Male population. Genes Immun 2012;13: 509-13.

Cited by

Sorted by citations

Authors
Bogaert, D. J. A., Dullaers, M., Lambrecht, B. N., Vermaelen, K. Y., De Baere, E., & Haerynck, F.
Affiliations
  • Ghent University Hospital (BE)
  • Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium
  • Ghent University (BE)
  • Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium
Corresponding author
Haerynck, Filomeen
ORCID
Venue
Journal of Medical Genetics
Publisher
BMJ
Published
2016-06-01
Volume
53
Issue
9
Pages
575-590
ISSN
  • 0022-2593 (ISSN-L)
  • 1468-6244
DOI
10.1136/jmedgenet-2015-103690
OpenAlex
W2415094030
Cited by
279
References
0
Citations by year
2026: 12 · 2025: 14 · 2024: 18 · 2023: 28 · 2022: 30 · 2021: 37 · 2020: 38 · 2019: 41 · 2018: 25 · 2017: 30 · 2016: 6
FWCI
3.28
Type
journal article
Language
en
Open access
Locations
  • Journal of Medical Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Fonds Wetenschappelijk Onderzoek
  • Vlaamse regering
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
Keywords
common variable immunodeficiency, primary antibody deficiency, genetic heterogeneity, ICOS, TACI, BAFF-R, CD21, CD20, CD27, IL-21, LRBA, CTLA-4, PIK3CD, PIK3R1, Vav1, Rac2, BLK, IKZF1, IRF2BP2, hypogammaglobulinemia, disease phenotypes, multifactorial inheritance
MeSH terms
Animals, Humans, Molecular Biology, Common Variable Immunodeficiency, Genetic Predisposition to Disease

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