{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:24:28Z","timestamp":1790979868951,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,2,27]]},"abstract":"<jats:p>\n                    Somatic mosaicism has been observed previously in the\n lymphocyte population of patients with Fanconi anemia (FA). To identify\n the cellular origin of the genotypic reversion, we examined each\n lymphohematopoietic and stromal cell lineage in an FA patient with a\n 2815\u20132816ins19 mutation in\n                    <jats:italic>FANCA<\/jats:italic>\n                    and known lymphocyte\n somatic mosaicism. DNA extracted from individually plucked peripheral\n blood T cell colonies and marrow colony-forming unit\n granulocyte\u2013macrophage and burst-forming unit erythroid cells revealed\n absence of the maternal\n                    <jats:italic>FANCA<\/jats:italic>\n                    exon 29 mutation in\n 74.0%, 80.3%, and 86.2% of colonies, respectively. These data,\n together with the absence of the\n                    <jats:italic>FANCA<\/jats:italic>\n                    exon 29 mutation\n in Epstein\u2013Barr virus-transformed B cells and its presence in\n fibroblasts, indicate that genotypic reversion, most likely because of\n back mutation, originated in a lymphohematopoietic stem cell and not\n solely in a lymphocyte population. Contrary to a predicted increase in\n marrow cellularity resulting from reversion in a hematopoietic stem\n cell, pancytopenia was progressive. Additional evaluations revealed a\n partial deletion of 11q in 3 of 20 bone marrow metaphase cells. By\n using interphase fluorescence\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization with\n an MLL gene probe mapped to band 11q23 to identify colony-forming unit\n granulocyte\u2013macrophage and burst-forming unit erythroid cells with the\n 11q deletion, the abnormal clone was exclusive to colonies with the\n                    <jats:italic>FANCA<\/jats:italic>\n                    exon 29 mutation. Thus, we demonstrate the\n spontaneous genotypic reversion in a lymphohematopoietic stem cell. The\n subsequent development of a clonal cytogenetic abnormality in\n nonrevertant cells suggests that\n                    <jats:italic>ex vivo<\/jats:italic>\n                    correction of\n hematopoietic stem cells by gene transfer may not be sufficient for\n providing life-long stable hematopoiesis in patients with FA.\n                  <\/jats:p>","DOI":"10.1073\/pnas.051609898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"2532-2537","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":190,"title":["Somatic mosaicism in Fanconi anemia: Evidence of genotypic reversion in lymphohematopoietic stem cells"],"prefix":"10.1073","volume":"98","author":[{"suffix":"Jr.","given":"John J.","family":"Gregory","sequence":"first","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Verlander","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orna","family":"Levran","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sat Dev","family":"Batish","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy R.","family":"Eide","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Steffenhagen","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arleen D.","family":"Auerbach","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Hematology, The Rockefeller\r University, 1230 York Avenue, New York, NY 10021;\r Department of Pediatrics and Blood and Marrow Transplant\r Program and Department of Laboratory Medicine and\r Pathology at the University of Minnesota School of Medicine,\r Minneapolis, MN 55455; and Department of Pediatrics,\r Memorial Sloan\u2013Kettering Cancer Center, 1275 York Avenue, New York, NY\r 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,2,13]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"753","volume-title":"The Metabolic and Molecular Basis of Inherited Diseases","author":"Auerbach A D","year":"2001","unstructured":"A D Auerbach, M Buchwald, H Joenje The Metabolic and Molecular Basis of Inherited Diseases, eds C R Scriver, A L Beadet, W S Sly, D Valle, B Childs, B Vogelstein (McGraw\u2013Hill, 8th Ed., New York), pp. 753\u2013768 (2001).","edition":"8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/303067"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-320"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-324"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0692-196"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9297(07)62959-0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/71626"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/3093"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.2.391.391"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-3-642-74179-1_6","volume-title":"Fanconi. 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