Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency
Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorph...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Tuovinen, Elina A. [verfasserIn] Grönholm, Juha [verfasserIn] Öhman, Tiina [verfasserIn] Pöysti, Sakari [verfasserIn] Toivonen, Raine [verfasserIn] Kreutzman, Anna [verfasserIn] Heiskanen, Kaarina [verfasserIn] Trotta, Luca [verfasserIn] Toiviainen-Salo, Sanna [verfasserIn] Routes, John M. [verfasserIn] Verbsky, James [verfasserIn] Mustjoki, Satu [verfasserIn] Saarela, Janna [verfasserIn] Kere, Juha [verfasserIn] Varjosalo, Markku [verfasserIn] Hänninen, Arno [verfasserIn] Seppänen, Mikko R. J. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
X-linked combined immunodeficiency diseases severe combined immunodeficiency, atypical |
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| Übergeordnetes Werk: |
Enthalten in: Journal of clinical immunology - Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981, 40(2020), 3 vom: 19. Feb., Seite 503-514 |
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| Übergeordnetes Werk: |
volume:40 ; year:2020 ; number:3 ; day:19 ; month:02 ; pages:503-514 |
| Links: |
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| DOI / URN: |
10.1007/s10875-020-00745-2 |
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| Katalog-ID: |
SPR039359468 |
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| 100 | 1 | |a Tuovinen, Elina A. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency |
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| 520 | |a Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. | ||
| 650 | 4 | |a X-linked combined immunodeficiency diseases |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a severe combined immunodeficiency, atypical |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a interleukin receptor common gamma subunit |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a endoplasmic reticulum |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Grönholm, Juha |e verfasserin |4 aut | |
| 700 | 1 | |a Öhman, Tiina |e verfasserin |4 aut | |
| 700 | 1 | |a Pöysti, Sakari |e verfasserin |4 aut | |
| 700 | 1 | |a Toivonen, Raine |e verfasserin |4 aut | |
| 700 | 1 | |a Kreutzman, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Heiskanen, Kaarina |e verfasserin |4 aut | |
| 700 | 1 | |a Trotta, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Toiviainen-Salo, Sanna |e verfasserin |4 aut | |
| 700 | 1 | |a Routes, John M. |e verfasserin |4 aut | |
| 700 | 1 | |a Verbsky, James |e verfasserin |4 aut | |
| 700 | 1 | |a Mustjoki, Satu |e verfasserin |4 aut | |
| 700 | 1 | |a Saarela, Janna |e verfasserin |4 aut | |
| 700 | 1 | |a Kere, Juha |e verfasserin |4 aut | |
| 700 | 1 | |a Varjosalo, Markku |e verfasserin |4 aut | |
| 700 | 1 | |a Hänninen, Arno |e verfasserin |4 aut | |
| 700 | 1 | |a Seppänen, Mikko R. J. |e verfasserin |4 aut | |
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10.1007/s10875-020-00745-2 doi (DE-627)SPR039359468 (SPR)s10875-020-00745-2-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Tuovinen, Elina A. verfasserin aut Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. X-linked combined immunodeficiency diseases (dpeaa)DE-He213 severe combined immunodeficiency, atypical (dpeaa)DE-He213 interleukin receptor common gamma subunit (dpeaa)DE-He213 endoplasmic reticulum (dpeaa)DE-He213 Golgi apparatus (dpeaa)DE-He213 Grönholm, Juha verfasserin aut Öhman, Tiina verfasserin aut Pöysti, Sakari verfasserin aut Toivonen, Raine verfasserin aut Kreutzman, Anna verfasserin aut Heiskanen, Kaarina verfasserin aut Trotta, Luca verfasserin aut Toiviainen-Salo, Sanna verfasserin aut Routes, John M. verfasserin aut Verbsky, James verfasserin aut Mustjoki, Satu verfasserin aut Saarela, Janna verfasserin aut Kere, Juha verfasserin aut Varjosalo, Markku verfasserin aut Hänninen, Arno verfasserin aut Seppänen, Mikko R. J. verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 3 vom: 19. Feb., Seite 503-514 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:3 day:19 month:02 pages:503-514 https://dx.doi.org/10.1007/s10875-020-00745-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 3 19 02 503-514 |
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10.1007/s10875-020-00745-2 doi (DE-627)SPR039359468 (SPR)s10875-020-00745-2-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Tuovinen, Elina A. verfasserin aut Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. X-linked combined immunodeficiency diseases (dpeaa)DE-He213 severe combined immunodeficiency, atypical (dpeaa)DE-He213 interleukin receptor common gamma subunit (dpeaa)DE-He213 endoplasmic reticulum (dpeaa)DE-He213 Golgi apparatus (dpeaa)DE-He213 Grönholm, Juha verfasserin aut Öhman, Tiina verfasserin aut Pöysti, Sakari verfasserin aut Toivonen, Raine verfasserin aut Kreutzman, Anna verfasserin aut Heiskanen, Kaarina verfasserin aut Trotta, Luca verfasserin aut Toiviainen-Salo, Sanna verfasserin aut Routes, John M. verfasserin aut Verbsky, James verfasserin aut Mustjoki, Satu verfasserin aut Saarela, Janna verfasserin aut Kere, Juha verfasserin aut Varjosalo, Markku verfasserin aut Hänninen, Arno verfasserin aut Seppänen, Mikko R. J. verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 3 vom: 19. Feb., Seite 503-514 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:3 day:19 month:02 pages:503-514 https://dx.doi.org/10.1007/s10875-020-00745-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 3 19 02 503-514 |
| allfields_unstemmed |
10.1007/s10875-020-00745-2 doi (DE-627)SPR039359468 (SPR)s10875-020-00745-2-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Tuovinen, Elina A. verfasserin aut Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. X-linked combined immunodeficiency diseases (dpeaa)DE-He213 severe combined immunodeficiency, atypical (dpeaa)DE-He213 interleukin receptor common gamma subunit (dpeaa)DE-He213 endoplasmic reticulum (dpeaa)DE-He213 Golgi apparatus (dpeaa)DE-He213 Grönholm, Juha verfasserin aut Öhman, Tiina verfasserin aut Pöysti, Sakari verfasserin aut Toivonen, Raine verfasserin aut Kreutzman, Anna verfasserin aut Heiskanen, Kaarina verfasserin aut Trotta, Luca verfasserin aut Toiviainen-Salo, Sanna verfasserin aut Routes, John M. verfasserin aut Verbsky, James verfasserin aut Mustjoki, Satu verfasserin aut Saarela, Janna verfasserin aut Kere, Juha verfasserin aut Varjosalo, Markku verfasserin aut Hänninen, Arno verfasserin aut Seppänen, Mikko R. J. verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 3 vom: 19. Feb., Seite 503-514 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:3 day:19 month:02 pages:503-514 https://dx.doi.org/10.1007/s10875-020-00745-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 3 19 02 503-514 |
| allfieldsGer |
10.1007/s10875-020-00745-2 doi (DE-627)SPR039359468 (SPR)s10875-020-00745-2-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Tuovinen, Elina A. verfasserin aut Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. X-linked combined immunodeficiency diseases (dpeaa)DE-He213 severe combined immunodeficiency, atypical (dpeaa)DE-He213 interleukin receptor common gamma subunit (dpeaa)DE-He213 endoplasmic reticulum (dpeaa)DE-He213 Golgi apparatus (dpeaa)DE-He213 Grönholm, Juha verfasserin aut Öhman, Tiina verfasserin aut Pöysti, Sakari verfasserin aut Toivonen, Raine verfasserin aut Kreutzman, Anna verfasserin aut Heiskanen, Kaarina verfasserin aut Trotta, Luca verfasserin aut Toiviainen-Salo, Sanna verfasserin aut Routes, John M. verfasserin aut Verbsky, James verfasserin aut Mustjoki, Satu verfasserin aut Saarela, Janna verfasserin aut Kere, Juha verfasserin aut Varjosalo, Markku verfasserin aut Hänninen, Arno verfasserin aut Seppänen, Mikko R. J. verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 3 vom: 19. Feb., Seite 503-514 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:3 day:19 month:02 pages:503-514 https://dx.doi.org/10.1007/s10875-020-00745-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 3 19 02 503-514 |
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10.1007/s10875-020-00745-2 doi (DE-627)SPR039359468 (SPR)s10875-020-00745-2-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Tuovinen, Elina A. verfasserin aut Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. X-linked combined immunodeficiency diseases (dpeaa)DE-He213 severe combined immunodeficiency, atypical (dpeaa)DE-He213 interleukin receptor common gamma subunit (dpeaa)DE-He213 endoplasmic reticulum (dpeaa)DE-He213 Golgi apparatus (dpeaa)DE-He213 Grönholm, Juha verfasserin aut Öhman, Tiina verfasserin aut Pöysti, Sakari verfasserin aut Toivonen, Raine verfasserin aut Kreutzman, Anna verfasserin aut Heiskanen, Kaarina verfasserin aut Trotta, Luca verfasserin aut Toiviainen-Salo, Sanna verfasserin aut Routes, John M. verfasserin aut Verbsky, James verfasserin aut Mustjoki, Satu verfasserin aut Saarela, Janna verfasserin aut Kere, Juha verfasserin aut Varjosalo, Markku verfasserin aut Hänninen, Arno verfasserin aut Seppänen, Mikko R. J. verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 3 vom: 19. Feb., Seite 503-514 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:3 day:19 month:02 pages:503-514 https://dx.doi.org/10.1007/s10875-020-00745-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 3 19 02 503-514 |
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Enthalten in Journal of clinical immunology 40(2020), 3 vom: 19. Feb., Seite 503-514 volume:40 year:2020 number:3 day:19 month:02 pages:503-514 |
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Enthalten in Journal of clinical immunology 40(2020), 3 vom: 19. Feb., Seite 503-514 volume:40 year:2020 number:3 day:19 month:02 pages:503-514 |
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X-linked combined immunodeficiency diseases severe combined immunodeficiency, atypical interleukin receptor common gamma subunit endoplasmic reticulum Golgi apparatus |
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Tuovinen, Elina A. @@aut@@ Grönholm, Juha @@aut@@ Öhman, Tiina @@aut@@ Pöysti, Sakari @@aut@@ Toivonen, Raine @@aut@@ Kreutzman, Anna @@aut@@ Heiskanen, Kaarina @@aut@@ Trotta, Luca @@aut@@ Toiviainen-Salo, Sanna @@aut@@ Routes, John M. @@aut@@ Verbsky, James @@aut@@ Mustjoki, Satu @@aut@@ Saarela, Janna @@aut@@ Kere, Juha @@aut@@ Varjosalo, Markku @@aut@@ Hänninen, Arno @@aut@@ Seppänen, Mikko R. J. @@aut@@ |
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|
| author |
Tuovinen, Elina A. |
| spellingShingle |
Tuovinen, Elina A. ddc 610 bkl 44.45 misc X-linked combined immunodeficiency diseases misc severe combined immunodeficiency, atypical misc interleukin receptor common gamma subunit misc endoplasmic reticulum misc Golgi apparatus Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency |
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Tuovinen, Elina A. |
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electronic Article |
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610 - Medicine & health |
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Not Illustrated |
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1573-2592 |
| topic_title |
610 ASE 44.45 bkl Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency X-linked combined immunodeficiency diseases (dpeaa)DE-He213 severe combined immunodeficiency, atypical (dpeaa)DE-He213 interleukin receptor common gamma subunit (dpeaa)DE-He213 endoplasmic reticulum (dpeaa)DE-He213 Golgi apparatus (dpeaa)DE-He213 |
| topic |
ddc 610 bkl 44.45 misc X-linked combined immunodeficiency diseases misc severe combined immunodeficiency, atypical misc interleukin receptor common gamma subunit misc endoplasmic reticulum misc Golgi apparatus |
| topic_unstemmed |
ddc 610 bkl 44.45 misc X-linked combined immunodeficiency diseases misc severe combined immunodeficiency, atypical misc interleukin receptor common gamma subunit misc endoplasmic reticulum misc Golgi apparatus |
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ddc 610 bkl 44.45 misc X-linked combined immunodeficiency diseases misc severe combined immunodeficiency, atypical misc interleukin receptor common gamma subunit misc endoplasmic reticulum misc Golgi apparatus |
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Elektronische Aufsätze Aufsätze Elektronische Ressource |
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Journal of clinical immunology |
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320573362 |
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610 - Medicine & health |
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Journal of clinical immunology |
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(DE-627)320573362 (DE-600)2016755-6 |
| title |
Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency |
| ctrlnum |
(DE-627)SPR039359468 (SPR)s10875-020-00745-2-e |
| title_full |
Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency |
| author_sort |
Tuovinen, Elina A. |
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Journal of clinical immunology |
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Journal of clinical immunology |
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eng |
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600 - Technology |
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2020 |
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txt |
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Tuovinen, Elina A. Grönholm, Juha Öhman, Tiina Pöysti, Sakari Toivonen, Raine Kreutzman, Anna Heiskanen, Kaarina Trotta, Luca Toiviainen-Salo, Sanna Routes, John M. Verbsky, James Mustjoki, Satu Saarela, Janna Kere, Juha Varjosalo, Markku Hänninen, Arno Seppänen, Mikko R. J. |
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40 |
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610 ASE 44.45 bkl |
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Elektronische Aufsätze |
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Tuovinen, Elina A. |
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10.1007/s10875-020-00745-2 |
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610 |
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verfasserin |
| title_sort |
novel hemizygous il2rg p.(pro58ser) mutation impairs il-2 receptor complex expression on lymphocytes causing x-linked combined immunodeficiency |
| title_auth |
Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency |
| abstract |
Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. |
| abstractGer |
Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. |
| abstract_unstemmed |
Abstract Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny. |
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| title_short |
Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency |
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https://dx.doi.org/10.1007/s10875-020-00745-2 |
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Grönholm, Juha Öhman, Tiina Pöysti, Sakari Toivonen, Raine Kreutzman, Anna Heiskanen, Kaarina Trotta, Luca Toiviainen-Salo, Sanna Routes, John M. Verbsky, James Mustjoki, Satu Saarela, Janna Kere, Juha Varjosalo, Markku Hänninen, Arno Seppänen, Mikko R. J. |
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Grönholm, Juha Öhman, Tiina Pöysti, Sakari Toivonen, Raine Kreutzman, Anna Heiskanen, Kaarina Trotta, Luca Toiviainen-Salo, Sanna Routes, John M. Verbsky, James Mustjoki, Satu Saarela, Janna Kere, Juha Varjosalo, Markku Hänninen, Arno Seppänen, Mikko R. J. |
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10.1007/s10875-020-00745-2 |
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2024-07-03T23:31:54.971Z |
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| score |
7.4006395 |