{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:20:15Z","timestamp":1790914815008,"version":"4.1.0"},"reference-count":81,"publisher":"American Society of Hematology","issue":"24","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The frequency of pathogenic\/likely pathogenic (P\/LP) germ line variants in patients with myelodysplastic syndrome (MDS) diagnosed at age 40 years or less is 15% to 20%. However, there are no comprehensive studies assessing the frequency of such variants across the age spectrum. We performed augmented whole-exome sequencing of peripheral blood samples from 404 patients with MDS and their related donors before allogeneic hematopoietic stem cell transplantation. Single-nucleotide and copy number variants in 233 genes were analyzed and interpreted. Germ line status was established by the presence of a variant in the patient and related donor or for those seen previously only as germ line alleles. We identified P\/LP germ line variants in 28 of 404 patients with MDS (7%), present within all age deciles. Patients with P\/LP variants were more likely to develop higher-grade MDS than those without (43% vs 25%; P\u00a0= .04). There was no statistically significant difference in outcome parameters between patients with and without a germ line variant, but the analysis was underpowered. P\/LP variants in bone marrow failure syndrome genes were found in 5 patients aged less than 40 years, whereas variants in DDX41 (n\u00a0= 4), telomere biology disorder genes (n\u00a0= 2), and general tumor predisposition genes (n\u00a0= 17) were found in patients aged more than 40\u00a0years. If presumed germ line variants were included, the yield of P\/LP variants would increase to 11%, and by adding suspicious variants of unknown significance, it would rise further to 12%. The high frequency of P\/LP germ line variants in our study supports comprehensive germ line genetic testing for all patients with MDS regardless of their age at diagnosis.<\/jats:p>","DOI":"10.1182\/blood.2022015790","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T20:12:29Z","timestamp":1660594349000},"page":"2533-2548","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":100,"title":["Germ line predisposition variants occur in\u00a0myelodysplastic syndrome patients of all ages"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9996-4277","authenticated-orcid":false,"given":"Simone","family":"Feurstein","sequence":"first","affiliation":[{"name":"1Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"},{"name":"2Section of Hematology, Oncology and Rheumatology, Department of Internal Medicine, Department of Medicine, Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9922-9232","authenticated-orcid":false,"given":"Amy M.","family":"Trottier","sequence":"additional","affiliation":[{"name":"1Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"},{"name":"3Division of Hematology, Department of Medicine, QEII Health Sciences Centre, Dalhousie University, Halifax, NS, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Estrada-Merly","sequence":"additional","affiliation":[{"name":"4Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Pozsgai","sequence":"additional","affiliation":[{"name":"1Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8255-6816","authenticated-orcid":false,"given":"Kelsey","family":"McNeely","sequence":"additional","affiliation":[{"name":"1Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-4106","authenticated-orcid":false,"given":"Michael W.","family":"Drazer","sequence":"additional","affiliation":[{"name":"1Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Ruhle","sequence":"additional","affiliation":[{"name":"5Section of General Surgery, Department of Surgery, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine","family":"Sadera","sequence":"additional","affiliation":[{"name":"1Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9956-1374","authenticated-orcid":false,"given":"Ashwin L.","family":"Koppayi","sequence":"additional","affiliation":[{"name":"1Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-7839","authenticated-orcid":false,"given":"Bart L.","family":"Scott","sequence":"additional","affiliation":[{"name":"6Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Oran","sequence":"additional","affiliation":[{"name":"7Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2621-7924","authenticated-orcid":false,"given":"Taiga","family":"Nishihori","sequence":"additional","affiliation":[{"name":"8Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Agrawal","sequence":"additional","affiliation":[{"name":"9Department of Hematology\/HCT, City of Hope Comprehensive Cancer Center and Beckman Research Institute of City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0003-0130","authenticated-orcid":false,"given":"Ayman","family":"Saad","sequence":"additional","affiliation":[{"name":"10Division of Hematology, The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9822-806X","authenticated-orcid":false,"given":"R. 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