{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tummala H"],"funding":["Medical Research Council","Blood Cancer UK"],"pagination":["17151-17155"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7382244"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["117(29)"],"pubmed_abstract":["Inherited bone marrow failure (BMF) syndromes are a heterogeneous group of diseases characterized by defective hematopoiesis and often predisposing to myelodysplastic syndrome (MDS) and acute myelogenous leukemia. We have studied a large family consisting of several affected individuals with hematologic abnormalities, including one family member who died of acute leukemia. By whole-exome sequencing, we identified a novel frameshift variant in the ubiquitously expressed transcription factor specificity protein 1 (<i>SP1</i>). This heterozygous variant (c.1995delA) truncates the canonical Sp1 molecule in the highly conserved C-terminal DNA-binding zinc finger domains. Transcriptomic analysis and gene promoter characterization in patients' blood revealed a hypermorphic effect of this Sp1 vari"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure."],"pmcid":["PMC7382244"],"funding_grant_id":["14032","MR/P018440/1"],"pubmed_authors":["Pontikos N","Sidhu JK","Ellison A","Bridger MG","Wang J","Rio-Machin A","Tummala H","Fitzgibbon J","Hasle H","Bewicke-Copley F","Dokal I","Walne AJ","Vulliamy T"],"additional_accession":[]},"is_claimable":false,"name":"A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure.","description":"Inherited bone marrow failure (BMF) syndromes are a heterogeneous group of diseases characterized by defective hematopoiesis and often predisposing to myelodysplastic syndrome (MDS) and acute myelogenous leukemia. We have studied a large family consisting of several affected individuals with hematologic abnormalities, including one family member who died of acute leukemia. By whole-exome sequencing, we identified a novel frameshift variant in the ubiquitously expressed transcription factor specificity protein 1 (<i>SP1</i>). This heterozygous variant (c.1995delA) truncates the canonical Sp1 molecule in the highly conserved C-terminal DNA-binding zinc finger domains. Transcriptomic analysis and gene promoter characterization in patients' blood revealed a hypermorphic effect of this Sp1 vari","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2026-05-04T03:43:34.165Z","creation":"2020-11-07T11:38:24Z"},"accession":"S-EPMC7382244","cross_references":{"pubmed":["32636268"],"doi":["10.1073/pnas.2002857117"]}}