Omenn Syndrome Caused by A Novel Mutation of the DCLRE1C Gene: Case Report and Review of Literature
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Abstract
We report a case of Omenn syndrome due to a novel mutation of the gene DCLRE1C(Artemis). He was referred to our hospital with a complaint of protracted diarrhea, erythematoexfoliative rash, urinary tract infection, pneumonia, and failure to thrive. He was 2 months old. At the first sight, the diagnoses of Omenn syndrome, graft versus host disease (GVHD), Netherton syndrome, and Atopic dermatitis came to mind. Laboratory evaluation showed lymphopenia, eosinophilia, high IgE, and whole-exome sequencing revealed a mutation of the DCLRE1C gene. After obtaining blood samples, he received broad-spectrum antibiotics, antifungals, antiviral, prophylaxis for pneumocystis Jirovecii pneumonia, and Intravenous immunoglobulin. He expired owing to delayed referral and overwhelming sepsis before receiving bone marrow transplantation. In every neonate infant presenting with erythematoexfoliative skin rash, refractory infection, and lymphopenia, Omenn syndrome should be considered.
1. Omenn GS. Familial Reticuloendotheliosis with Eosinophilia. N Engl J Med. 1965;273:427-32.
2. Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Bjorkman A, et al. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. Hum Mol Genet. 2015;24(25):7361-72.
3. van der Burg M, Gennery AR. Educational paper. The expanding clinical and immunological spectrum of severe combined immunodeficiency. Eur J Pediatr. 2011;170(5):561-71.
4. Ijspeert H, Lankester AC, van den Berg JM, Wiegant W, van Zelm MC, Weemaes CM, et al. Artemis splice defects cause atypical SCID and can be restored in vitro by an antisense oligonucleotide. Genes Immun. 2011;12(6):434-44.
5. Villa A, Notarangelo LD. RAG gene defects at the verge of immunodeficiency and immune dysregulation. Immunol Rev. 2019;287(1):73-90.
6. Delmonte OM, Schuetz C, Notarangelo LD. RAG Deficiency: Two Genes, Many Diseases. J Clin Immunol. 2018;38(6):646-55.
7. Kato M, Kimura H, Seki M, Shimada A, Hayashi Y, Morio T, et al. Omenn syndrome--review of several phenotypes of Omenn syndrome and RAG1/RAG2 mutations in Japan. Allergol Int. 2006;55(2):115-9.
8. Lee PP, Woodbine L, Gilmour KC, Bibi S, Cale CM, Amrolia PJ, et al. The many faces of Artemis-deficient combined immunodeficiency - Two patients with DCLRE1C mutations and a systematic literature review of genotype-phenotype correlation. Clin Immunol. 2013;149(3):464-74.
9. Ma Y, Pannicke U, Schwarz K, Lieber MR. Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell. 2002;108(6):781-94.
10. de Villartay JP. V(D)J recombination deficiencies. Adv Exp Med Biol. 2009;650:46-58.
11. Mansilla-Soto J, Cortes P. VDJ recombination: Artemis and its in vivo role in hairpin opening. J Exp Med. 2003;197(5):543-7.
12. Wong SY, Lu CP, Roth DB. A RAG1 mutation found in Omenn syndrome causes coding flank hypersensitivity: a novel mechanism for antigen receptor repertoire restriction. J Immunol. 2008;181(6):4124-30.
13. Roifman CM, Zhang J, Atkinson A, Grunebaum E, Mandel K. Adenosine deaminase deficiency can present with features of Omenn syndrome. J Allergy Clin Immunol. 2008;121(4):1056-8.
14. Ibusuki A, Nishikawa T, Hiraki T, Okano T, Imai K, Kanegane H, et al. Prominent dermal Langerhans cells in an Omenn syndrome patient with a novel mutation in the IL2RG gene. J Dermatol. 2019;46(11):1019-23.
15. Gennery AR, Slatter MA, Rice J, Hoefsloot LH, Barge D, McLean-Tooke A, et al. 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. 2008;153(1):75-80.
16. Henderson LA, Frugoni F, Hopkins G, Al-Herz W, Weinacht K, Comeau AM, et al. First reported case of Omenn syndrome in a patient with reticular dysgenesis. J Allergy Clin Immunol. 2013;131(4):1227-30, 30 e1-3.
17. Roifman CM, Gu Y, Cohen A. Mutations in the RNA component of RNase mitochondrial RNA processing might cause Omenn syndrome. J Allergy Clin Immunol. 2006;117(4):897-903.
18. Giliani S, Bonfim C, de Saint Basile G, Lanzi G, Brousse N, Koliski A, et al. Omenn syndrome in an infant with IL7RA gene mutation. J Pediatr. 2006;148(2):272-4.
19. Walkovich K, Vander Lugt M. ZAP70-Related Combined Immunodeficiency. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews((R)). Seattle (WA): University of Washington, Seattle
Copyright © 1993-2022, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.
20. Grunebaum E, Bates A, Roifman CM. Omenn syndrome is associated with mutations in DNA ligase IV. J Allergy Clin Immunol. 2008;122(6):1219-20.
21. Villa A, Notarangelo LD, Roifman CM. Omenn syndrome: inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol. 2008;122(6):1082-6.
22. Omenn Syndrome [Internet]. 2022. Available from: https://omim.org/entry/603554.
23. Daley A, Andreae DA, Horwitz A. Not just a rash diagnosis! The allergist's role in improving recognition of Omenn syndrome. Ann Allergy Asthma Immunol. 2020;125(3):244-46 e1.
24. Felgentreff K, Lee YN, Frugoni F, Du L, van der Burg M, Giliani S, et al. Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency. J Allergy Clin Immunol. 2015;136(1):140-50 e7.
25. Li L, Moshous D, Zhou Y, Wang J, Xie G, Salido E, et al. A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans. J Immunol. 2002;168(12):6323-9.
26. Noordzij JG, Verkaik NS, van der Burg M, van Veelen LR, de Bruin-Versteeg S, Wiegant W, et al. Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow. Blood. 2003;101(4):1446-52.
27. Moshous D, Pannetier C, Chasseval Rd R, Deist Fl F, Cavazzana-Calvo M, Romana S, et al. Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. J Clin Invest. 2003;111(3):381-7.
28. Ege M, Ma Y, Manfras B, Kalwak K, Lu H, Lieber MR, et al. Omenn syndrome due to ARTEMIS mutations. Blood. 2005;105(11):4179-86.
29. Lo YM, Lo ES, Watson N, Noakes L, Sargent IL, Thilaganathan B, et al. Two-way cell traffic between mother and fetus: biologic and clinical implications. Blood. 1996;88(11):4390-5.
30. Muller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001;98(6):1847-51.
31. Tallar M, Routes J. Omenn Syndrome Identified by Newborn Screening. Clin Perinatol. 2020;47(1):77-86.
32. Hamamy H. Consanguineous marriages : Preconception consultation in primary health care settings. J Community Genet. 2012;3(3):185-92.
33. Al-Herz W, Aldhekri H, Barbouche MR, Rezaei N. Consanguinity and primary immunodeficiencies. Hum Hered. 2014;77(1-4):138-43.
34. Arkwright PD, Gennery AR. Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci. 2011;1238:7-14.
2. Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Bjorkman A, et al. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. Hum Mol Genet. 2015;24(25):7361-72.
3. van der Burg M, Gennery AR. Educational paper. The expanding clinical and immunological spectrum of severe combined immunodeficiency. Eur J Pediatr. 2011;170(5):561-71.
4. Ijspeert H, Lankester AC, van den Berg JM, Wiegant W, van Zelm MC, Weemaes CM, et al. Artemis splice defects cause atypical SCID and can be restored in vitro by an antisense oligonucleotide. Genes Immun. 2011;12(6):434-44.
5. Villa A, Notarangelo LD. RAG gene defects at the verge of immunodeficiency and immune dysregulation. Immunol Rev. 2019;287(1):73-90.
6. Delmonte OM, Schuetz C, Notarangelo LD. RAG Deficiency: Two Genes, Many Diseases. J Clin Immunol. 2018;38(6):646-55.
7. Kato M, Kimura H, Seki M, Shimada A, Hayashi Y, Morio T, et al. Omenn syndrome--review of several phenotypes of Omenn syndrome and RAG1/RAG2 mutations in Japan. Allergol Int. 2006;55(2):115-9.
8. Lee PP, Woodbine L, Gilmour KC, Bibi S, Cale CM, Amrolia PJ, et al. The many faces of Artemis-deficient combined immunodeficiency - Two patients with DCLRE1C mutations and a systematic literature review of genotype-phenotype correlation. Clin Immunol. 2013;149(3):464-74.
9. Ma Y, Pannicke U, Schwarz K, Lieber MR. Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell. 2002;108(6):781-94.
10. de Villartay JP. V(D)J recombination deficiencies. Adv Exp Med Biol. 2009;650:46-58.
11. Mansilla-Soto J, Cortes P. VDJ recombination: Artemis and its in vivo role in hairpin opening. J Exp Med. 2003;197(5):543-7.
12. Wong SY, Lu CP, Roth DB. A RAG1 mutation found in Omenn syndrome causes coding flank hypersensitivity: a novel mechanism for antigen receptor repertoire restriction. J Immunol. 2008;181(6):4124-30.
13. Roifman CM, Zhang J, Atkinson A, Grunebaum E, Mandel K. Adenosine deaminase deficiency can present with features of Omenn syndrome. J Allergy Clin Immunol. 2008;121(4):1056-8.
14. Ibusuki A, Nishikawa T, Hiraki T, Okano T, Imai K, Kanegane H, et al. Prominent dermal Langerhans cells in an Omenn syndrome patient with a novel mutation in the IL2RG gene. J Dermatol. 2019;46(11):1019-23.
15. Gennery AR, Slatter MA, Rice J, Hoefsloot LH, Barge D, McLean-Tooke A, et al. 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. 2008;153(1):75-80.
16. Henderson LA, Frugoni F, Hopkins G, Al-Herz W, Weinacht K, Comeau AM, et al. First reported case of Omenn syndrome in a patient with reticular dysgenesis. J Allergy Clin Immunol. 2013;131(4):1227-30, 30 e1-3.
17. Roifman CM, Gu Y, Cohen A. Mutations in the RNA component of RNase mitochondrial RNA processing might cause Omenn syndrome. J Allergy Clin Immunol. 2006;117(4):897-903.
18. Giliani S, Bonfim C, de Saint Basile G, Lanzi G, Brousse N, Koliski A, et al. Omenn syndrome in an infant with IL7RA gene mutation. J Pediatr. 2006;148(2):272-4.
19. Walkovich K, Vander Lugt M. ZAP70-Related Combined Immunodeficiency. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews((R)). Seattle (WA): University of Washington, Seattle
Copyright © 1993-2022, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.
20. Grunebaum E, Bates A, Roifman CM. Omenn syndrome is associated with mutations in DNA ligase IV. J Allergy Clin Immunol. 2008;122(6):1219-20.
21. Villa A, Notarangelo LD, Roifman CM. Omenn syndrome: inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol. 2008;122(6):1082-6.
22. Omenn Syndrome [Internet]. 2022. Available from: https://omim.org/entry/603554.
23. Daley A, Andreae DA, Horwitz A. Not just a rash diagnosis! The allergist's role in improving recognition of Omenn syndrome. Ann Allergy Asthma Immunol. 2020;125(3):244-46 e1.
24. Felgentreff K, Lee YN, Frugoni F, Du L, van der Burg M, Giliani S, et al. Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency. J Allergy Clin Immunol. 2015;136(1):140-50 e7.
25. Li L, Moshous D, Zhou Y, Wang J, Xie G, Salido E, et al. A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans. J Immunol. 2002;168(12):6323-9.
26. Noordzij JG, Verkaik NS, van der Burg M, van Veelen LR, de Bruin-Versteeg S, Wiegant W, et al. Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow. Blood. 2003;101(4):1446-52.
27. Moshous D, Pannetier C, Chasseval Rd R, Deist Fl F, Cavazzana-Calvo M, Romana S, et al. Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. J Clin Invest. 2003;111(3):381-7.
28. Ege M, Ma Y, Manfras B, Kalwak K, Lu H, Lieber MR, et al. Omenn syndrome due to ARTEMIS mutations. Blood. 2005;105(11):4179-86.
29. Lo YM, Lo ES, Watson N, Noakes L, Sargent IL, Thilaganathan B, et al. Two-way cell traffic between mother and fetus: biologic and clinical implications. Blood. 1996;88(11):4390-5.
30. Muller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001;98(6):1847-51.
31. Tallar M, Routes J. Omenn Syndrome Identified by Newborn Screening. Clin Perinatol. 2020;47(1):77-86.
32. Hamamy H. Consanguineous marriages : Preconception consultation in primary health care settings. J Community Genet. 2012;3(3):185-92.
33. Al-Herz W, Aldhekri H, Barbouche MR, Rezaei N. Consanguinity and primary immunodeficiencies. Hum Hered. 2014;77(1-4):138-43.
34. Arkwright PD, Gennery AR. Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci. 2011;1238:7-14.
| Files | ||
| Issue | Vol 4, No 3 (2021) | |
| Section | Review Article | |
| DOI | https://doi.org/10.18502/igj.v4i3.12113 | |
| Keywords | ||
| DCLRE1C Mutation Omenn Syndrome Erythematoexfoliative Rash Esosinophilia | ||
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How to Cite
1.
Cheraghi T, Safaee A, Esmaili E, Golshekan kiomars, ghavideldarestani M. Omenn Syndrome Caused by A Novel Mutation of the DCLRE1C Gene: Case Report and Review of Literature. Immunol Genet J. 2021;4(3):132-137.
