{"doi":"10.1002/ajmg.a.63454","title":"Probable digenic inheritance of <scp>Diamond–Blackfan</scp> anemia","abstract":"A 26-year-old female proband with a clinical diagnosis and consistent phenotype of Diamond-Blackfan anemia (DBA, OMIM 105650) without an identified genotype was referred to the Undiagnosed Diseases Network. DBA is classically associated with monoallelic variants that have an autosomal-dominant or -recessive mode of inheritance. Intriguingly, her case was solved by a detection of a digenic interaction between non-allelic RPS19 and RPL27 variants. This was confirmed with a machine learning structural model, co-segregation analysis, and RNA sequencing. This is the first report of DBA caused by a digenic effect of two non-allelic variants demonstrated by machine learning structural model. This case suggests that atypical phenotypic presentations of DBA may be caused by digenic inheritance in some individuals. We also conclude that a machine learning structural model can be useful in detecting digenic models of possible interactions between products encoded by alleles of different genes inherited from non-affected carrier parents that can result in DBA with an unrealized 25% recurrence risk.","journal":"American Journal of Medical Genetics Part A","year":2023,"id":375866,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":921462,"name":"Rory J. Tinker","orcid":"0000-0001-7093-8844","position":1,"is_corresponding":false},{"id":426774,"name":"Alican Gulsevin","orcid":"0000-0002-8724-5777","position":2,"is_corresponding":false},{"id":1134196,"name":"Serena Neumann","orcid":"0009-0001-0957-7338","position":3,"is_corresponding":false},{"id":364733,"name":"Rizwan Hamid","orcid":"0000-0001-5063-7614","position":4,"is_corresponding":false},{"id":308564,"name":"Joy D. Cogan","orcid":"0000-0001-8106-1216","position":5,"is_corresponding":false},{"id":1134657,"name":"Lynette Rives","orcid":null,"position":6,"is_corresponding":false},{"id":323892,"name":"Qi Liu","orcid":"0000-0002-0839-8039","position":7,"is_corresponding":false},{"id":210547,"name":"Hua-Chang Chen","orcid":"0000-0003-0497-2483","position":8,"is_corresponding":false},{"id":507191,"name":"Karen M. Joos","orcid":"0000-0002-6210-4126","position":9,"is_corresponding":false},{"id":365769,"name":"John A. Phillips","orcid":null,"position":10,"is_corresponding":false},{"id":1134658,"name":"the Undiagnosed Diseases Network","orcid":null,"position":11,"is_corresponding":false},{"id":1134195,"name":"Yutaka Furuta","orcid":"0009-0001-7278-8242","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T01:16:23.381203Z","pmid":"37897121","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":[]}