{"doi":"10.1182/blood.2022015790","title":"Germ line predisposition variants occur in myelodysplastic syndrome patients of all ages","abstract":"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 = .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 = 4), telomere biology disorder genes (n = 2), and general tumor predisposition genes (n = 17) were found in patients aged more than 40 years. 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.","journal":"Blood","year":2022,"id":234831,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":90,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":851381,"name":"Amy M. 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Coleman Lindsley","orcid":"0000-0001-9822-806X","position":14,"is_corresponding":false},{"id":284156,"name":"Ryotaro Nakamura","orcid":"0000-0002-9082-0680","position":15,"is_corresponding":false},{"id":348722,"name":"Soyoung Kim","orcid":"0000-0003-1404-0575","position":16,"is_corresponding":false},{"id":284115,"name":"Zhen‐Huan Hu","orcid":"0000-0002-3303-8991","position":17,"is_corresponding":false},{"id":278923,"name":"Ronald Sobecks","orcid":"0000-0003-1608-3261","position":18,"is_corresponding":false},{"id":122974,"name":"Stephen R. Spellman","orcid":"0000-0002-7271-8252","position":19,"is_corresponding":false},{"id":122972,"name":"Wael Saber","orcid":"0000-0002-6544-5815","position":20,"is_corresponding":false},{"id":438090,"name":"Lucy A. 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