{"doi":"10.1084/jem.20210444","title":"Familial thrombocytopenia due to a complex structural variant resulting in a <i>WAC-ANKRD26</i> fusion transcript","abstract":"Advances in genome sequencing have resulted in the identification of the causes for numerous rare diseases. However, many cases remain unsolved with standard molecular analyses. We describe a family presenting with a phenotype resembling inherited thrombocytopenia 2 (THC2). THC2 is generally caused by single nucleotide variants that prevent silencing of ANKRD26 expression during hematopoietic differentiation. Short-read whole-exome and genome sequencing approaches were unable to identify a causal variant in this family. Using long-read whole-genome sequencing, a large complex structural variant involving a paired-duplication inversion was identified. Through functional studies, we show that this structural variant results in a pathogenic gain-of-function WAC-ANKRD26 fusion transcript. Our findings illustrate how complex structural variants that may be missed by conventional genome sequencing approaches can cause human disease.","journal":"The Journal of Experimental Medicine","year":2021,"id":167247,"datarank":1.1287572790088523,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.6042811447888801,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.6042811447888801,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":25,"citers_with_citation_signal":22,"citers_with_endowment":22,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":42105,"name":"Jeffrey M. Verboon","orcid":"0000-0002-4454-6043","position":1,"is_corresponding":false},{"id":3035,"name":"Leif S. Ludwig","orcid":"0000-0002-2916-2164","position":2,"is_corresponding":false},{"id":694096,"name":"Susan Black","orcid":"0000-0002-0209-6283","position":3,"is_corresponding":false},{"id":15484,"name":"Wendy Luo","orcid":"0000-0002-7041-823X","position":4,"is_corresponding":false},{"id":70601,"name":"Kopal Garg","orcid":"0000-0003-0124-7710","position":5,"is_corresponding":false},{"id":17311,"name":"Richard A. Voit","orcid":"0000-0002-6790-8641","position":6,"is_corresponding":false},{"id":970,"name":"Ryan L. Collins","orcid":"0000-0003-1268-9995","position":7,"is_corresponding":false},{"id":58439,"name":"Kiran Garimella","orcid":"0000-0002-6212-5736","position":8,"is_corresponding":false},{"id":53889,"name":"Maura Costello","orcid":"0000-0002-0281-3035","position":9,"is_corresponding":false},{"id":457095,"name":"Katherine R. Chao","orcid":"0000-0003-2897-2410","position":10,"is_corresponding":false},{"id":5011,"name":"Julia K. Goodrich","orcid":"0000-0003-0480-1924","position":11,"is_corresponding":false},{"id":364149,"name":"Stephanie DiTroia","orcid":"0000-0002-6847-6780","position":12,"is_corresponding":false},{"id":995,"name":"Anne H. O’Donnell-Luria","orcid":"0000-0001-6418-9592","position":13,"is_corresponding":false},{"id":1025,"name":"Michael E. Talkowski","orcid":"0000-0003-2889-0992","position":14,"is_corresponding":false},{"id":420376,"name":"Alan D. Michelson","orcid":"0000-0002-1746-4819","position":15,"is_corresponding":false},{"id":37476,"name":"Alan Cantor","orcid":"0000-0002-5136-028X","position":16,"is_corresponding":false},{"id":17323,"name":"Vijay G. Sankaran","orcid":"0000-0003-0044-443X","position":17,"is_corresponding":false},{"id":17321,"name":"Lara Wahlster","orcid":"0000-0001-8409-7580","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:45:54.042727Z","pmid":"33857290","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}