Novel LRBA Mutation and Possible Germinal Mosaicism in a Slavic Family

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References

  1. 1.

    Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM, Phadwal K, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet. 2012;90:986–1001.

  2. 2.

    Burns SO, Zenner HL, Plagnol V, Curtis J, Mok K, Eisenhut M, et al. LRBA gene deletion in a patient presenting with autoimmunity without hypogammaglobulinemia. J Allergy Clin Immunol. 2012;130(6):1428–32.

  3. 3.

    Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P, Yazdani R, et al. Clinical, immunological, molecular analyses and outcomes of Iranian patients with LRBA deficiency: a longitudinal study. Pediatr Allergy Immunol. 2017;28(5):478–84.

  4. 4.

    Alkhairy OK, Abolhassani H, Rezaei N, Fang M, Andersen KK, Chavoshzadeh Z, et al. Spectrum of phenotypes associated with mutations in LRBA. J Clin Immunol. 2016;36(1):33–45.

  5. 5.

    Seidel MG, Böhm K, Dogu F, Worth A, Thrasher A, Florkin B, et al. Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency with allogeneic hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2017;141:770–775.e1. https://doi.org/10.1016/j.jaci.2017.04.023.

  6. 6.

    Kostel Bal S, Haskologlu S, Serwas NK, Islamoglu C, Aytekin C, Kendirli T, et al. Multiple presentations of LRBA deficiency: a single-center experience. J Clin Immunol. 2017;37:790–800. https://doi.org/10.1007/s10875-017-0446-y.

  7. 7.

    Gámez-Díaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG, Noriko M, et al. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016;137(1):223–30.

  8. 8.

    Charbonnier LM, Janssen E, Chou J, Ohsumi TK, Keles S, Hsu JT, et al. 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(1):217–27.

  9. 9.

    Johnson MB, De Franco E, Lango Allen H, Al Senani A, Elbarbary N, Siklar Z, et al. Recessively inherited LRBA mutations cause autoimmunity presenting as neonatal diabetes. Diabetes. 2017;66(8):2316–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. 10.

    Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, et al. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science. 2015;349(6246):436–40.

    Article  PubMed  CAS  Google Scholar 

  11. 11.

    Schreiner F, Plamper M, Dueker G, Schoenberger S, Gámez-Díaz L, Grimbacher B, et al. Infancy-onset T1DM, short stature, and severe immunodysregulation in two siblings with a homozygous LRBA mutation. J Clin Endocrinol Metab. 2016;101(3):898–904.

  12. 12.

    Bratanič N, Kovač J, Pohar K, Trebušak Podkrajšek K, Ihan A, Battelino T, et al. Multifocal gastric adenocarcinoma in a patient with LRBA deficiency. Orphanet J Rare Dis. 2017;12(1):131.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Al Sukaiti N, Abdel Rahman K, Al Shekaili J, Al Oraimi S, Al Sinani A, Al Rahbi N, et al. Agammaglobulinaemia despite terminal B-cell differentiation in a patient with a novel LRBA mutation. Clin Transl Immunology. 2017;6(5):e144.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. 14.

    Alroqi FJ, Charbonnier LM, Baris S, Kiykim A, Chou J, Platt CD, et al. Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation. J Allergy Clin Immunol. 2017;141:1050–1059.e10. https://doi.org/10.1016/j.jaci.2017.05.022.

  15. 15.

    Sari S, Dogu F, Hwa V, Haskologlu S, Dauber A, Rosenfeld R, et al. A successful HSCT in a girl with novel LRBA mutation with refractory celiac disease. J Clin Immunol. 2016;36(1):8–11.

  16. 16.

    Alangari A, Alsultan A, Adly N, Massaad MJ, Kiani IS, Aljebreen A, et al. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol. 2012;130(2):481–8.

  17. 17.

    Bakhtiar S, Ruemmele F, Charbit-Henrion F, Lévy E, Rieux-Laucat F, Cerf-Bensussan N, et al. Atypical manifestation of LPS-responsive beige-like anchor deficiency syndrome as an autoimmune endocrine disorder without enteropathy and immunodeficiency. Front Pediatr. 2016;4:98.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Seidel MG, Hirschmugl T, Gamez-Diaz L, Schwinger W, Serwas N, Deutschmann A, et al. Long-term remission after allogeneic hematopoietic stem cell transplantation in LPS-responsive beige-like anchor (LRBA) deficiency. J Allergy Clin Immunol. 2015;135(5):1384–90.

  19. 19.

    Tesi B, Priftakis P, Lindgren F, Chiang SC, Kartalis N, Löfstedt A, et al. Successful hematopoietic stem cell transplantation in a patient with LPS-responsive beige-like anchor (LRBA) gene mutation. J Clin Immunol. 2016;36(5):480–9.

    Article  PubMed  CAS  Google Scholar 

  20. 20.

    Levy E, Stolzenberg MC, Bruneau J, Breton S, Neven B, Sauvion S, et al. LRBA deficiency with autoimmunity and early onset chronic erosive polyarthritis. Clin Immunol. 2016;168:88–93.

    Article  PubMed  CAS  Google Scholar 

  21. 21.

    Revel-Vilk S, Fischer U, Keller B, Nabhani S, Gámez-Díaz L, Rensing-Ehl A, et al. Autoimmune lymphoproliferative syndrome-like disease in patients with LRBA mutation. Clin Immunol. 2015;159(1):84–92.

  22. 22.

    Besnard C, Levy E, Aladjidi N, Stolzenberg MC, Magerus-Chatinet A, Alibeu O, et al. Pediatric-onset Evans syndrome: heterogeneous presentation and high frequency of monogenic disorders including LRBA and CTLA4 mutations. Clin Immunol. 2018;188:52–7.

  23. 23.

    Lappalainen I, Almeida-King J, Kumanduri V, Senf A, Spalding JD, Ur-Rehman S, et al. The European Genome-phenome Archive of human data consented for biomedical research. Nat Genet. 2015;47(7):692–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. 24.

    Anazi S, Al-Sabban E, Alkuraya FS. Gonadal mosaicism as a rare cause of autosomal recessive inheritance. Clin Genet. 2014;85(3):278–81.

    Article  PubMed  CAS  Google Scholar 

  25. 25.

    Lucas CL, Kuehn HS, Zhao F, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110d result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15:88–97.

    Article  PubMed  CAS  Google Scholar 

  26. 26.

    Segundo GRS, Takano OA, Moraes LSL, Nadaf MISV, Fernandes SJ, Ochs HD, et al. Paternal gonadal mosaicism as cause of a puzzling inheritance pattern of activated PI3-kinase delta syndrome. Ann Allergy Asthma Immunol. 2017;119(6):564–6.

  27. 27.

    Maglione PJ, Overbey JR, Cunningham-Rundles C. Progression of common variable immunodeficiency interstitial lung disease accompanies distinct pulmonary and laboratory findings. J Allergy Clin Immunol Pract. 2015;3(6):941–50.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Haapaniemi EM, Kaustio M, Rajala HL, van Adrichem AJ, Kainulainen L, Glumoff V, et al. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3. Blood. 2015;125(4):639–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgments

We sincerely thank all our patients and their family members for their trust, cooperation, and consent to perform genetic and functional assays and the referring doctors for their help. We are also grateful to doctor Polina Stepensky and Professor Markus Seidel for the consultation on our Pt2.

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Correspondence to Svetlana O. Sharapova.

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The authors declare that they have no conflicts of interest.

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Sharapova, S.O., Haapaniemi, E., Sakovich, I.S. et al. Novel LRBA Mutation and Possible Germinal Mosaicism in a Slavic Family. J Clin Immunol 38, 471–474 (2018). https://doi.org/10.1007/s10875-018-0515-x

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Keywords

  • LRBA homozygous mutation
  • multiple autoimmunity
  • germline mosaicism
  • Slavic family