{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:14:44Z","timestamp":1790500484789,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mutations of the IL2RG gene, which encodes for the interleukin-2 receptor common gamma chain (\u03b3C, CD132), can lead to X-linked severe combined immunodeficiency (X-SCID) associated with a T\u2212B+NK\u2212 phenotype as a result of dysfunctional \u03b3C-JAK3-STAT5 signaling. Lately, hypomorphic mutations of the IL2RG gene have been described causing atypical SCID with a milder phenotype. Here, we report three brothers with low-normal lymphocyte counts and susceptibility to recurrent respiratory infections and cutaneous warts. The clinical presentation combined with dysgammaglobulinemia suspected an inherited immunity disorder, which has been proven by Next Generation Sequencing as a novel c.458T &gt; C; p.Ile153Thr IL2RG missense-mutation. Subsequent functional characterization revealed impaired T-cell proliferation, low TREC levels and a skewed TCR V\u03b2 repertoire in all three patients. Interestingly, investigation of various subpopulations showed normal expression of CD132 but with partially impaired STAT5 phosphorylation compared to healthy controls. Additionally, we performed precise genetic analysis of subpopulations revealing spontaneous somatic reversion, predominately in lymphoid derived CD3+, CD4+ and CD8+ T cells. Our data demonstrate that the atypical SCID phenotype noticed in these three brothers is due to the combination of hypomorphic IL-2RG function and somatic reversion.<\/jats:p>","DOI":"10.3390\/genes13010035","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T10:16:18Z","timestamp":1640254578000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Somatic Reversion of a Novel IL2RG Mutation Resulting in Atypical X-Linked Combined Immunodeficiency"],"prefix":"10.3390","volume":"13","author":[{"given":"Yujuan","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Peter","family":"Gratz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Ure\u00f1a-Bail\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Gratz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8041-055X","authenticated-orcid":false,"given":"Karin","family":"Schilbach-St\u00fcckle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Renno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derya","family":"G\u00fcng\u00f6r","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8527-4278","authenticated-orcid":false,"given":"Daniel A.","family":"Mader","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Malenke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin S.","family":"Antony","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"Handgretinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0211-2343","authenticated-orcid":false,"given":"Markus","family":"Mezger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Hematology and Oncology, University Children\u2019s Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/hmg\/2.8.1099","article-title":"The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1","volume":"2","author":"Puck","year":"1993","journal-title":"Hum. 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