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Immunological aspects of 22q11.2 deletion syndrome

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Abstract

Chromosome 22q11 deletion is the most common chromosomal deletion syndrome and is found in the majority of patients with DiGeorge syndrome and velo-cardio-facial syndrome. Patients with CHARGE syndrome may share similar features. Cardiac malformations, speech delay, and immunodeficiency are the most common manifestations. The immunological phenotype may vary widely between patients. Severe T lymphocyte immunodeficiency is rare—thymic transplantation offers a new approach to treatment, as well as insights into thymic physiology and central tolerance. Combined partial immunodeficiency is more common, leading to recurrent sinopulmonary infection in early childhood. Autoimmunity is an increasingly recognized complication. New insights into pathophysiology are reviewed.

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References

  1. Kobrynski LJ, Sullivan KE (2007) Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370:1443–1452

    Article  PubMed  CAS  Google Scholar 

  2. Perez E, Sullivan KE (2002) Chromosome 22q11.2 deletion syndrome (DiGeorge and velocardiofacial syndromes). Curr Opin Pediatr 14:678–683

    Article  PubMed  Google Scholar 

  3. Shprintzen RJ, Higgins AM, Antshel K, Fremont W, Roizen N, Kates W (2005) Velo-cardio-facial syndrome. Curr Opin Pediatr 17:725–730

    Article  PubMed  Google Scholar 

  4. Yamagashi H, Srivastava D (2003) Unravelling the genetic and developmental mysteries of 22q11 deletion syndrome. Trends Mol Med 9:383–389

    Article  Google Scholar 

  5. Jerome LA, Papaioannou VE (2001) DiGeorge syndrome phenotype in mice mutant for the T box gene, Tbx1. Nat Genet 27:286–291

    Article  PubMed  CAS  Google Scholar 

  6. Cooper MD, Peterson RDA, Good RA (1965) A new concept of the cellular basis of immunity. J Pediatr 67:907–908

    Article  Google Scholar 

  7. de la Chapelle A, Herva R, Koivisto M, Aula P (1981) A deletion in chromosome 22 can cause DiGeorge syndrome. Hum Genet 57:253–256

    Google Scholar 

  8. Kelley RI, Zackai EH, Emanuel BS, Kistenmacher M, Greenberg F, Punnett HH (1982) The association of the DiGeorge anomalad with partial monosomy of chromosome 22. J Pediatr 101:197–200

    Article  PubMed  CAS  Google Scholar 

  9. Driscoll DA, Spinner NB, Budarf ML, McDonald-McGinn DM, Zackai EH, Goldberg RB, Shprintzen RJ, Saal HM, Zonana J, Jones MC (1992) Deletions and microdeletions of 22q11.2 in velo-cardio-fa-cial syndrome. Am J Med Genet 44:261–268

    Article  PubMed  CAS  Google Scholar 

  10. Matsuoka R, Takao A, Kimura M, Imamura S, Kondo C, Joh-o K, Ikeda K, Nishibatake M, Ando M, Momma K (1994) Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2. Am J Med Genet 53:285–289

    Article  PubMed  CAS  Google Scholar 

  11. McDonald-McGinn DM, Driscoll DA, Bason L, Christensen K, Lynch D, Sullivan K, Canning D, Zavod W, Quinn N, Rome J (1995) Autosomal dominant “Opitz” GBBB syndrome due to a 22q11.2 deletion. Am J Med Genet 59:103–113

    Article  PubMed  CAS  Google Scholar 

  12. Devriendt K, Swillen A, Fryns JP (1998) Deletion in chromosome region 22q11 in a child with CHARGE association. Clin Genet 53:408–410

    Article  PubMed  CAS  Google Scholar 

  13. Yagi H, Furutani Y, Hamada H, Sasaki T, Asakawa S, Minoshima S, Ichida F, Joo K, Kimura M, Imamura S, Kamatani N, Momma K, Takao A, Nakazawa M, Shimizu N, Matsuoka R (2003) Role of TBX1 in human del22q11.2 syndrome. Lancet 362:1366–1373

    Article  PubMed  CAS  Google Scholar 

  14. Greenberg F, Valdes C, Rosenblatt HM, Kirkland JL, Ledbetter DH (1986) Hypoparathyroidism and T cell immune defect in a patient with 10p deletion syndrome. J Pediatr 109:489–492

    Article  PubMed  CAS  Google Scholar 

  15. Monaco G, Ciccimarra F, Pignata C, Garofalo S (1989) T cell immunodeficiency in a patient with 10p deletion syndrome. J Pediatr 115:330

    PubMed  CAS  Google Scholar 

  16. Monaco G, Pignata C, Rossi E, Mascellaro O, Cocozza S, Ciccimarra F (1991) DiGeorge anomaly associated with 10p deletion. Am J Med Genet 39:215–216

    Article  PubMed  CAS  Google Scholar 

  17. Sullivan KE, Jawad AF, Randall P, Driscoll DA, Emanuel BS, McDonald-McGinn DM, Zackai EH (1998) Lack of correlation between impaired T cell production, immunodeficiency, and other phenotypic features in chromosome 22q11.2 deletion syndromes. Clin Immunol Immunopathol 86:141–146

    Article  PubMed  CAS  Google Scholar 

  18. Johnson D, Morrison N, Grant L, Turner T, Fantes J, Connor JM, Murday V (2006) Confirmation of CHD7 as a cause of CHARGE association identified by mapping a balanced chromosome translocation in affected monozygotic twins. J Med Genet 43:280–284

    Article  PubMed  CAS  Google Scholar 

  19. Gennery AR, Slatter MA, Rice J, Hoefsloot LH, Barge D, McLean-Tooke A, Montgomery T, Goodship JA, Burt AD, Flood TJ, Abinun M, Cant AJ, Johnson D (2008) Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell+ severe combined immune deficiency and may cause Omenn-like syndrome. Clin Exp Immunol 153:75–80

    Article  PubMed  CAS  Google Scholar 

  20. Carlson C, Sirotkin H, Pandita R, Goldberg R, McKie J, Wadey R, Patanjali SR, Weissman SM, Anyane-Yeboa K, Warburton D, Scrambler P, Shprintzen R, Kucherlapati R, Morrow BE (1997) Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients. Am J Hum Genet 61:620–629

    Article  PubMed  CAS  Google Scholar 

  21. Edelmann L, Pandita RK, Morrow BE (1999) Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am J Hum Genet 64:1076–1086

    Article  PubMed  CAS  Google Scholar 

  22. Meechan DW, Maynard TM, Gopalakrishna D, Wu Y, LaMantia AS (2007) When half is not enough: gene expression and dosage in the 22q11 deletion syndrome. Gene Expr 13:299–310

    Article  PubMed  CAS  Google Scholar 

  23. Taddei I, Morishima M, Huynh T, Lindsay EA (2001) Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes. Proc Natl Acad Sci USA 98:11428–11431

    Article  PubMed  CAS  Google Scholar 

  24. Schinke M, Izumo S (2001) Deconstructing DiGeorge syndrome. Nat Genet 27:238–240

    Article  PubMed  CAS  Google Scholar 

  25. Jerome LA, Papaioannou VE (2001) DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet 27:286–291

    Article  PubMed  CAS  Google Scholar 

  26. Guris DL, Fantes J, Tara D, Druker BJ, Imamoto A (2001) Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nat Genet 27:293–298

    Article  PubMed  CAS  Google Scholar 

  27. Guris DL, Duester G, Papaioannou VE, Imamoto A (2006) Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Dev Cell 10:81–92

    Article  PubMed  CAS  Google Scholar 

  28. van Bueren KL, Papangeli I, Rochais F, Pearce K, Roberts C, Calmont A, Szumska D, Kelly RG, Bhattacharya S, Scambler PJ (2010) Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome. Dev Biol 340:369–380

    Article  PubMed  Google Scholar 

  29. Marfella CG, Imbalzano AN (2007) The Chd family of chromatin remodelers. Mutat Res 618:30–40

    Article  PubMed  CAS  Google Scholar 

  30. Sillibourne JE, Delaval B, Redick S, Sinah M, Doxsey SJ (2007) Chromatin remodeling proteins interact with pericentrin to regulate centrosome integrity. Mol Biol Cell 18:3667–3680

    Article  PubMed  CAS  Google Scholar 

  31. Aramaki M, Kimura T, Udaka T, Kosaki R, Mitsuhashi T, Okada Y, Takahashi T, Kosaki K (2007) Embryonic expression profile of chicken CHD7, the ortholog of the causative gene for CHARGE syndrome. Birth Defects Res A Clin Mol Teratol 79:50–57

    Article  PubMed  CAS  Google Scholar 

  32. Sanlaville D, Etchevers HC, Gonzales M, Martinovic J, Clément-Ziza M, Delezoide AL, Aubry MC, Pelet A, Chemouny S, Cruaud C, Audollent S, Esculpavit C, Goudefroye G, Ozilou C, Fredouille C, Joye N, Morichon-Delvallez N, Dumez Y, Weissenbach J, Munnich A, Amiel J, Encha-Razavi F, Lyonnet S, Vekemans M, Attié-Bitach T (2006) Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development. J Med Genet 43:211–217

    Article  PubMed  CAS  Google Scholar 

  33. de Lonlay-Debeney P, Cormier-Daire V, Amiel J, Abadie V, Odent S, Paupe A, Couderc S, Tellier AL, Bonnet D, Prieur M, Vekemans M, Munnich A, Lyonnet S (1997) Features of DiGeorge syndrome and CHARGE association in five patients. J Med Genet 34:986–989

    Article  PubMed  Google Scholar 

  34. Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC (2007) Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood 109:4539–4547

    Article  PubMed  CAS  Google Scholar 

  35. Holländer G, Gill J, Zuklys S, Iwanami N, Liu C, Takahama Y (2006) Cellular and molecular events during early thymus development. Immunol Rev 209:28–46

    Article  PubMed  Google Scholar 

  36. Le Lievre CS, Le Douarin NM (1975) Mesenchymal derivatives of the neural crest: analysis of chimeric quail and chick embryos. J Embryol Exp Morphol 34:125–154

    PubMed  CAS  Google Scholar 

  37. Haynes BF, Heinly CS (1995) Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment. J Exp Med 181:1445–1458

    Article  PubMed  CAS  Google Scholar 

  38. Poliani PL, Facchetti F, Ravanini M, Gennery AR, Villa A, Roifman CM, Notarangelo LD (2009) Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome. Blood 114:105–108

    Article  PubMed  CAS  Google Scholar 

  39. Gill J, Malin M, Sutherland J, Gray D, Hollander G, Boyd R (2003) Thymic generation and regeneration. Immunol Rev 195:28–50

    Article  PubMed  CAS  Google Scholar 

  40. Akiyama T, Shimo Y, Yanai H, Qin J, Ohshima D, Maruyama Y, Asaumi Y, Kitazawa J, Takayanagi H, Penninger JM, Matsumoto M, Nitta T, Takahama Y, Inoue J (2008) The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 29:423–437

    Article  PubMed  CAS  Google Scholar 

  41. Zuklys S, Balciunaite G, Agarwal A, Fasler-Kan E, Palmer E, Holländer GA (2000) Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). J Immunol 165:1976–1983

    PubMed  CAS  Google Scholar 

  42. Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu YJ (2005) Hassall’s corpuscles instruct dendritic cells to induce CD4+ CD25+ regulatory T cells in human thymus. Nature 436:1181–1185

    Article  PubMed  CAS  Google Scholar 

  43. Müller SM, Kohn T, Schulz AS, Debatin KM, Friedrich W (2000) Similar pattern of thymic-dependent T-cell reconstitution in infants with severe combined immunodeficiency after human leukocyte antigen (HLA)-identical and HLA-nonidentical stem cell transplantation. Blood 96:4344–4349

    PubMed  Google Scholar 

  44. Consortium ***Finnish-German APECED (1997) An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet 17:399–403

    Article  Google Scholar 

  45. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27:20–21

    Article  PubMed  CAS  Google Scholar 

  46. Poliani PL, Vermi W, Facchetti F (2009) Thymus microenvironment in human primary immunodeficiency diseases. Curr Opin Allergy Clin Immunol 9:489–495

    Article  PubMed  Google Scholar 

  47. Writzl K, Cale CM, Pierce CM, Wilson LC, Hennekam RC (2007) Immunological abnormalities in CHARGE syndrome. Eur J Med Genet 50:338–345

    Article  PubMed  Google Scholar 

  48. Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, Schuffenhauer S, Oechsler H, Belohradsky B, Prieur M, Aurias A, Raymond FL, Clayton-Smith J, Hatchwell E, McKeown C, Beemer FA, Dallapiccola B, Novelli G, Hurst JA, Ignatius J, Green AJ, Winter RM, Brueton L, Brøndum-Nielsen K, Scambler PJ (1997) Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 34:798–804

    Article  PubMed  CAS  Google Scholar 

  49. Barber JCK, Walker JM, Barker MR, McNinch AW, Hallett RJ (1996) Repeated cytogenetic culture failure as an indicator of immunodeficiency. Lancet 348:1518

    Article  PubMed  CAS  Google Scholar 

  50. Ocejo-Vinyals JG, Lozano MJ, Sánchez-Velasco P, Escribano de Diego J, Paz-Miguel JE, Leyva-Cobián F (2000) An unusual concurrence of graft versus host disease caused by engraftment of maternal lymphocytes with DiGeorge anomaly. Arch Dis Child 83:165–169

    Article  PubMed  CAS  Google Scholar 

  51. Müller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W (2001) Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood 98:1847–1851

    Article  PubMed  Google Scholar 

  52. Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, Sempowski GD, Rhein ME, Szabolcs P, Hale LP, Buckley RH, Coyne KE, Rice HE, Mahaffey SM, Skinner MA (2004) Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases. J Allergy Clin Immunol 113:734–741

    Article  PubMed  CAS  Google Scholar 

  53. Janda A, Sedlacek P, Hönig M, Friedrich W, Champagne M, Matsumoto T, Fischer A, Neven B, Contet A, Bensoussan D, Bordigoni P, Loeb D, Savage W, Jabado N, Bonilla FA, Slatter MA, Davies EG, Gennery AR (2010) Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood 116:2229–2236

    Article  PubMed  CAS  Google Scholar 

  54. McGhee SA, Lloret MG, Stiehm ER (2009) Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol Res 45:37–45

    Article  PubMed  Google Scholar 

  55. Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, Amrolia PJ, Gaspar HB, Davies EG, Friedrich W, Hoenig M, Notarangelo LD, Mazzolari E, Porta F, Bredius RG, Lankester AC, Wulffraat NM, Seger R, Güngör T, Fasth A, Sedlacek P, Neven B, Blanche S, Fischer A, Cavazzana-Calvo M, Landais P, Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation, European Society for Immunodeficiency (2010) Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol 126, 602-10.e1-11

  56. Neven B, Leroy S, Decaluwe H, Le Deist F, Picard C, Moshous D, Mahlaoui N, Debré M, Casanova JL, Dal Cortivo L, Madec Y, Hacein-Bey-Abina S, de Saint Basile G, de Villartay JP, Blanche S, Cavazzana-Calvo M, Fischer A (2009) Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency. Blood 113:4114–4124

    Article  PubMed  CAS  Google Scholar 

  57. Cleveland WW, Fogel BJ, Brown WT, Kay HE (1968) Foetal thymic transplant in a case of DiGeorge’s syndrome. Lancet (7580), 1211–1214

  58. August CS, Berkel AI, Levey RH, Rosen FS, Kay HE (1970). Establishment of immunological competence in a child with congenital thymic aplasia by a graft of fetal thymus. Lancet (7656):1080–1083

  59. Markert ML, Boeck A, Hale LP, Kloster AL, McLaughlin TM, Batchvarova MN, Douek DC, Koup RA, Kostyu DD, Ward FE, Rice HE, Mahaffey SM, Schiff SE, Buckley RH, Haynes BF (1999) Transplantation of thymus tissue in complete DiGeorge syndrome. N Engl J Med 341:1180–1189

    Article  PubMed  CAS  Google Scholar 

  60. Markert ML, Devlin BH, McCarthy EA (2010) Thymus transplantation. Clin Immunol 135:236–246

    Article  PubMed  CAS  Google Scholar 

  61. Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, Le Deist F, Alexieff MJ, Li J, Hauser ER, Haynes BF, Rice HE, Skinner MA, Mahaffey SM, Jaggers J, Stein LD, Mill MR (2003) Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood 102:1121–1130

    Article  PubMed  CAS  Google Scholar 

  62. Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, Sedlak DA, Sempowski GD, Hale LP, Rice HE, Mahaffey SM, Skinner MA (2004) Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood 104:2574–2581

    Article  PubMed  CAS  Google Scholar 

  63. Chinn IK, Devlin BH, Li YJ, Markert ML (2008) Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol 126:277–281

    Article  PubMed  CAS  Google Scholar 

  64. Markert ML, Devlin BH, Chinn IK, McCarthy EA, Li YJ (2008) Factors affecting success of thymus transplantation for complete DiGeorge anomaly. Am J Transplant 8:1729–1736

    Article  PubMed  CAS  Google Scholar 

  65. Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC (2003) Aire regulates negative selection of organ-specific T cells. Nat Immunol 4:350–354

    Article  PubMed  CAS  Google Scholar 

  66. Anderson MS, Venanzi ES, Chen Z, Berzins SP, Benoist C, Mathis D (2005) The cellular mechanism of Aire control of T cell tolerance. Immunity 23:227–239

    Article  PubMed  CAS  Google Scholar 

  67. Li W, Kim MG, Gourley TS, McCarthy BP, Sant’Angelo DB, Chang CH (2005) An alternate pathway for CD4 T cell development: thymocyte-expressed MHC class II selects a distinct T cell population. Immunity 23:375–386

    Article  PubMed  CAS  Google Scholar 

  68. Choi EY, Jung KC, Park HJ, Chung DH, Song JS, Yang SD, Simpson E, Park SH (2005) Thymocyte–thymocyte interaction for efficient positive selection and maturation of CD4 T cells. Immunity 23:387–396

    Article  PubMed  CAS  Google Scholar 

  69. Junker AK, Driscoll DA (1995) Humoral immunity in DiGeorge syndrome. J Pediatr 127:231–237

    Article  PubMed  CAS  Google Scholar 

  70. Sullivan KE, McDonald-McGinn D, Driscoll DA, Emanuel BS, Zackai EH, Jawad AF (1999) Longitudinal analysis of lymphocyte function and numbers in the first year of life in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Diagn Lab Immunol 6:906–911

    PubMed  CAS  Google Scholar 

  71. Jawad AF, McDonald-Mcginn DM, Zackai E, Sullivan KE (2001) Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr 139:715–723

    Article  PubMed  CAS  Google Scholar 

  72. Cancrini C, Romiti ML, Finocchi A, Di Cesare S, Ciaffi P, Capponi C, Pahwa S, Rossi P (2005) Post-natal ontogenesis of the T-cell receptor CD4 and CD8 Vbeta repertoire and immune function in children with DiGeorge syndrome. J Clin Immunol 25:265–274

    Article  PubMed  CAS  Google Scholar 

  73. McLean-Tooke A, Barge D, Spickett GP, Gennery AR (2008) Immunological defects in 22q11.2 deletion syndrome. J Allergy Clin Immunol 122:362–367

    Article  PubMed  CAS  Google Scholar 

  74. Lima K, Abrahamsen TG, Foelling I, Natvig S, Ryder LP, Olaussen RW (2010) Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+ CD45RA+ T cell counts and T cell receptor rearrangement excision circles. Clin Exp Immunol 161:98–107

    PubMed  CAS  Google Scholar 

  75. Piliero LM, Sanford AN, McDonald-McGinn DM, Zackai EH, Sullivan KE (2004) T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome. Blood 103:1020–1025

    Article  PubMed  CAS  Google Scholar 

  76. Pierdominic IM, Mazzetta F, Caprini E, Marziali M, Digilio MC, Marino B, Aiuti A, Amati F, Russo G, Novelli G, Pandolfi F, Luzi G, Giovannetti A (2003) Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Exp Immunol 132:323–331

    Article  Google Scholar 

  77. Sedivá A, Bartůnková J, Zachová R, Poloucková A, Hrusák O, Janda A, Kocárek E, Novotná D, Novotná K, Klein T (2005) Early development of immunity in DiGeorge syndrome. Med Sci Monit 11: CR182–187

    Google Scholar 

  78. Eberle P, Berger C, Junge S, Dougoud S, Büchel EV, Riegel M, Schinzel A, Seger R, Güngör T (2009) Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11.2 microdeletion and partial DiGeorge syndrome. Clin Exp Immunol 155:189–198

    Article  PubMed  CAS  Google Scholar 

  79. Herwadkar A, Gennery AR, Moran AS, Haeney MR, Arkwright PD (2010) Association between hypoparathyroidism and defective T cell immunity in 22q11.2 deletion syndrome. J Clin Pathol 63:151–155

    Article  PubMed  CAS  Google Scholar 

  80. Kung SJ, Gripp KW, Stephan MJ, Fairchok MP, McGeady SJ (2007) Selective IgM deficiency and 22q11.2 deletion syndrome. Ann Allergy Asthma Immunol 99:87–92

    Article  PubMed  Google Scholar 

  81. Finocchi A, Di Cesare S, Romiti ML, Capponi C, Rossi P, Carsetti R, Cancrini C (2006) Humoral immune responses and CD27+ B cells in children with DiGeorge syndrome (22q11.2 deletion syndrome). Pediatr Allergy Immunol 17:382–388

    Article  PubMed  CAS  Google Scholar 

  82. Schubert MS, Moss RB (1992) Selective polysaccharide antibody deficiency in familial DiGeorge syndrome. Ann Allergy 69:231–238

    PubMed  CAS  Google Scholar 

  83. Gennery AR, Barge D, O’Sullivan JJ, Flood TJ, Abinun M, Cant AJ (2002) Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome. Arch. Dis Child 86:422–425

    Article  CAS  Google Scholar 

  84. Brown JJ, Datta V, Browning MJ, Swift PJF (2004) Graves’ disease in Di George Syndrome: Patient report with a review of endocrine autoimmunity associated with 22q11.2 deletion. J Pediatr Endocrinol Metab 17: 1575–1579

    Google Scholar 

  85. Smith CA, Driscoll DA, Emmanuel BS, McDonald-McGinn DM, Zackai EH, Sullivan KE (1998) Increased prevalence of immunoglobulin A deficiency in patients with a chromosome 22q11.2 deletion syndrome (DiGeorge Syndrome/ Velo-Cardio-Facial Syndrome). Clin Diagn Lab Immunol 5:415–417

    PubMed  CAS  Google Scholar 

  86. Davies K, Stiehm RE, Woo P, Murray KJ (2001) Juvenile idiopathic polyarticular arthritis and IGA deficiency in the 22q11 deletion syndrome. J Rheumatol 28:2326–2334

    PubMed  CAS  Google Scholar 

  87. Haire RN, Buell RD, Litman RT, Ohta Y, Fu SM, Honjo T, Matsuda F, de la Morena M, Carro J, Good RA, Litman GW (1993) Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome. J Exp Med 178:825–834

    Article  PubMed  CAS  Google Scholar 

  88. Perez EE, Bokszczanin A, McDonald-McGinn D, Zackai EH, Sullivan KE (2003) Safety of live viral vaccines in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Pediatrics 112:e325

    Article  PubMed  Google Scholar 

  89. Moylett EH, Wasan AN, Noroski LM, Shearer WT (2004) Live viral vaccines in patients with partial DiGeorge syndrome: clinical experience and cellular immunity. Clin Immunol 112:106–112

    Article  PubMed  CAS  Google Scholar 

  90. Azzari C, Gambineri E, Resti M, Moriondo M, Betti L, Saldias LRG, Gelli AM, Vierucci A (2005) Safety and immunogenicity of measles-mumps-rubella vaccine in children with congenital immunodeficiency (DiGeorge syndrome). Vaccine 23:1668–1671

    Article  PubMed  CAS  Google Scholar 

  91. Waters V, Peterson KS, LaRussa P (2007) Live viral vaccines in a DiGeorge syndrome patient. Arch Dis Child 92:519–520

    Article  PubMed  CAS  Google Scholar 

  92. Davis CM, Kancherla VS, Reddy A, Chan W, Yeh HW, Noroski LM, Rosenblatt H, Shearer WT, Chinen J (2008) Development of specific T-cell responses to Candida and tetanus antigens in partial DiGeorge syndrome. J Allergy Clin Immunol 122:1194–1199

    Article  PubMed  CAS  Google Scholar 

  93. Al-Sukaiti N, Reid B, Lavi S, Al-Zaharani D, Atkinson A, Roifman CM, Grunebaum E (2010) Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome. J Allergy Clin Immunol 126:868–869

    Article  PubMed  Google Scholar 

  94. Kratz CP, Niehues T, Lyding S, Heusch A, Janssen G, Gobel U (2003) Evans Syndrome in a patient with Chromosome 22q11.2 deletion syndrome: a case report. Pediatr Hematol Oncol 20:167–172

    Article  PubMed  CAS  Google Scholar 

  95. Rasmussen SA, Williams CA, Ayoube M, Sleasman JW, Gray BA, Bent-Williams A, Stalker HJ, Zorir T (1996) Juvenile rheumatoid arthritis in velo-cardio-facial syndrome: coincidence or unusual complication. Am J Med Genet 64:546–550

    Article  PubMed  CAS  Google Scholar 

  96. DePiero AD, Louire EM, Berman BW, Robin NH, Zinn EB, Hostoffer RW (1997) Recurrent immune cytopenias in 2 patients with Di George/velo cardio facial syndrome. J Paediatr 13:484–486

    Article  Google Scholar 

  97. Verloes A, Curry C, Jamar M, Herens C, O’Lague P, Marks J, Sarda P, Blanchet P (1998) Juvenile rheumatoid arthritis and del (22q11) syndrome: a non-random association. J Med Genet 35:943–947

    Article  PubMed  CAS  Google Scholar 

  98. Bach JF (2005) Infections and autoimmune diseases. J Autoimmun 25(Suppl):74–80

    Article  PubMed  CAS  Google Scholar 

  99. Schurman SH, Candotti F (2003) Autoimmunity in Wiskott-Aldrich syndrome. Curr Opin Rheumatol 15:446–453

    Article  PubMed  CAS  Google Scholar 

  100. Zemble R, Luning Prak E, McDonald K, McDonald-McGinn D, Zackai E, Sullivan K (2010) Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Immunol 136:409–418

    Article  PubMed  CAS  Google Scholar 

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  1. Institute of Cellular Medicine, Old Children’s Outpatients, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK

    A. R. Gennery

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Gennery, A.R. Immunological aspects of 22q11.2 deletion syndrome. Cell. Mol. Life Sci. 69, 17–27 (2012). https://doi.org/10.1007/s00018-011-0842-z

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  • DOI: https://doi.org/10.1007/s00018-011-0842-z

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