RAG1 Reversion Mosaicism in a Patient with Omenn Syndrome

被引:16
作者
Crestani, Elena [1 ]
Choo, Sharon [2 ]
Frugoni, Francesco [1 ]
Lee, Yu Nee [1 ]
Richards, Stephanie [2 ]
Smart, Joanne [2 ]
Notarangelo, Luigi D. [1 ]
机构
[1] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA
[2] Royal Childrens Hosp, Dept Allergy & Immunol, Parkville, Vic 3052, Australia
关键词
Omenn syndrome; RAG1; somatic reversion; severe combined immune deficiency; T cell repertoire; SEVERE COMBINED IMMUNODEFICIENCY; SOMATIC MOSAICISM; T-CELLS; DEFICIENCY; PHENOTYPE; MUTATION;
D O I
10.1007/s10875-014-0051-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To identify mechanisms of disease in a child born to consanguineous parents, who presented with Omenn syndrome (OS) and was found to carry a heterozygous RAG1 mutation in peripheral blood DNA. Mutation analysis was performed on whole blood and buccal swab DNA. Recombination activity of the mutant RAG1 protein and diversity of T cell repertoire were tested. Apparent heterozygosity for a novel, functionally null RAG1 mutation in peripheral blood DNA from a patient with OS was shown to be secondary to true somatic reversion. Analysis of T cell repertoire demonstrated expression of various TCRBV families, but an overall restricted pattern. This is the first case of true somatic reversion of a RAG1 mutation in a patient with OS. The reversion event likely occurred at a stage where only a limited pool of T cell progenitors capable of performing V(D)J recombination could be generated. This work emphasizes the importance of performing functional studies to investigate the significance of novel genetic variants, and to consider somatic reversion as a possible disease modifier in SCID.
引用
收藏
页码:551 / 554
页数:4
相关论文
共 9 条
  • [1] Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency
    Hirschhorn, R
    Yang, DRX
    Puck, JM
    Huie, ML
    Jiang, CK
    Kurlandsky, LE
    [J]. NATURE GENETICS, 1996, 13 (03) : 290 - 295
  • [2] Multiple Reversions of an IL2RG Mutation Restore T cell Function in an X-linked Severe Combined Immunodeficiency Patient
    Kawai, Tomoki
    Saito, Megumu
    Nishikomori, Ryuta
    Yasumi, Takahiro
    Izawa, Kazushi
    Murakami, Tomohiko
    Okamoto, Shigefumi
    Mori, Yasuko
    Nakagawa, Noriko
    Imai, Kohsuke
    Nonoyama, Shigeaki
    Wada, Taizo
    Yachie, Akihiro
    Ohmori, Katsuyuki
    Nakahata, Tatsutoshi
    Heike, Toshio
    [J]. JOURNAL OF CLINICAL IMMUNOLOGY, 2012, 32 (04) : 690 - 697
  • [3] A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency
    Lee, Yu Nee
    Frugoni, Francesco
    Dobbs, Kerry
    Walter, Jolan E.
    Giliani, Silvia
    Gennery, Andrew R.
    Al-Herz, Waleed
    Haddad, Elie
    LeDeist, Francoise
    Bleesing, Jack H.
    Henderson, Lauren A.
    Pai, Sung-Yun
    Nelson, Robert P.
    El-Ghoneimy, Dalia H.
    El-Feky, Reem A.
    Reda, Shereen M.
    Hossny, Elham
    Soler-Palacin, Pere
    Fuleihan, Ramsay L.
    Patel, Niraj C.
    Massaad, Michel J.
    Geha, Raif S.
    Puck, Jennifer M.
    Palma, Paolo
    Cancrini, Caterina
    Chen, Karin
    Vihinen, Mauno
    Alt, Frederick W.
    Notarangelo, Luigi D.
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2014, 133 (04) : 1099 - +
  • [4] Somatic Mosaicism Caused by Monoallelic Reversion of a Mutation in T Cells of a Patient with ADA-SCID and the Effects of Enzyme Replacement Therapy on the Revertant Phenotype
    Moncada-Velez, M.
    Velez-Ortega, A.
    Orrego, J.
    Santisteban, I.
    Jagadeesh, J.
    Olivares, M.
    Olaya, N.
    Hershfield, M.
    Candotti, F.
    Franco, J.
    [J]. SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2011, 74 (05) : 471 - 481
  • [5] Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: The Primary Immune Deficiency Treatment Consortium experience
    Shearer, William T.
    Dunn, Elizabeth
    Notarangelo, Luigi D.
    Dvorak, Christopher C.
    Puck, Jennifer M.
    Logan, Brent R.
    Griffith, Linda M.
    Kohn, Donald B.
    O'Reilly, Richard J.
    Fleisher, Thomas A.
    Pai, Sung-Yun
    Martinez, Caridad A.
    Buckley, Rebecca H.
    Cowan, Morton J.
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2014, 133 (04) : 1092 - 1098
  • [6] Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells
    Stephan, V
    Wahn, V
    LeDeist, F
    Dirksen, U
    Broker, B
    MullerFleckenstein, I
    Horneff, G
    Schroten, H
    Fischer, A
    Basile, GD
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (21) : 1563 - 1567
  • [7] Omenn syndrome: Inflammation in leaky severe combined immunodeficiency
    Villa, Anna
    Notarangelo, Luigi D.
    Roifman, Chaim M.
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 122 (06) : 1082 - 1086
  • [8] Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency
    Wada, T
    Toma, T
    Okamoto, H
    Kasahara, Y
    Koizumi, S
    Agematsu, K
    Kimura, H
    Shimada, A
    Hayashi, Y
    Kato, M
    Yachie, A
    [J]. BLOOD, 2005, 106 (06) : 2099 - 2101
  • [9] Somatic mosaicism in primary immune deficiencies
    Wada, Taizo
    Candotti, Fabio
    [J]. CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 8 (06) : 510 - 514