{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:14:31Z","timestamp":1781108071387,"version":"3.54.1"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,7,17]]},"abstract":"<jats:p>\n                    Somatic mosaicism caused by\n                    <jats:italic>in vivo<\/jats:italic>\n                    reversion of inherited mutations has been described in several human genetic disorders. Back mutations resulting in restoration of wild-type sequences and second-site mutations leading to compensatory changes have been shown in mosaic individuals. In most cases, however, the precise genetic mechanisms underlying the reversion events have remained unclear, except for the few instances where crossing over or gene conversion have been demonstrated. Here, we report a patient affected with Wiskott\u2013Aldrich syndrome (WAS) caused by a 6-bp insertion (ACGAGG) in the WAS protein gene, which abrogates protein expression. Somatic mosaicism was documented in this patient whose majority of T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same six nucleotides. These findings strongly suggest that DNA polymerase slippage was the cause of the original germ-line insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the propositus T cell progenitors, thus leading to reversion mosaicism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.151260498","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"8697-8702","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":124,"title":["Somatic mosaicism in Wiskott\u2013Aldrich syndrome suggests\n                    <i>in vivo<\/i>\n                    reversion by a DNA slippage mechanism"],"prefix":"10.1073","volume":"98","author":[{"given":"Taizo","family":"Wada","sequence":"first","affiliation":[{"name":"Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; and Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shepherd H.","family":"Schurman","sequence":"additional","affiliation":[{"name":"Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; and Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Otsu","sequence":"additional","affiliation":[{"name":"Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; and Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth K.","family":"Garabedian","sequence":"additional","affiliation":[{"name":"Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; and Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans D.","family":"Ochs","sequence":"additional","affiliation":[{"name":"Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; and Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; and Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Candotti","sequence":"additional","affiliation":[{"name":"Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; and Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,7,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)82002-5"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00792601"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90528-2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.1.70"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118712"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.905"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0796-290"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199611213352104"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.8.5245"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117509"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81894-2"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1159\/000484749"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051609898"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4338"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/11956"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000734"},{"key":"e_1_3_3_17_2","first-page":"203","volume":"4","author":"Levinson G","year":"1987","unstructured":"G Levinson, G A Gutman Mol Biol Evol 4, 203\u2013221 (1987).","journal-title":"Mol Biol Evol"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.10.3797.bloodjournal86103797"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300926"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.1119"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199704000-00013"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.9.3008.409a10_3008_3016"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4706"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.4049\/jimmunol.151.8.4383","volume":"151","author":"Molina I J","year":"1993","unstructured":"I J Molina, J Sancho, C Terhorst, F S Rosen, E Remold-O'Donnell J Immunol 151, 4383\u20134390 (1993).","journal-title":"J Immunol"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.9.1329"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(80)90429-8"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V72.5.1735.1735"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(89)90315-7"},{"key":"e_1_3_3_29_2","first-page":"271","volume":"4","author":"Mantuano E","year":"1993","unstructured":"E Mantuano, F Candotti, S Giliani, O Parolini, M Lusardi, M Zucchi, A Lanfranchi, F Porta, P Airo, A Albertini, et al. 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