{"doi":"10.1002/ajmg.a.61962","title":"Discovery of a novel <scp><i>CHD7</i> CHARGE</scp> syndrome variant by integrated omics analyses","abstract":"Chromodomain helicase DNA-binding protein 7 (CHD7) pathogenic variants are identified in more than 90% of infants and children with CHARGE (Coloboma of the iris, retina, and/or optic disk; congenital Heart defects, choanal Atresia, Retardation of growth and development, Genital hypoplasia, and characteristic outer and inner Ear anomalies and deafness) syndrome. Approximately, 10% of cases have no known genetic cause identified. We report a male child with clinical features of CHARGE syndrome and nondiagnostic genetic testing that included chromosomal microarray, CHD7 sequencing and deletion/duplication analysis, SEMA3E sequencing, and trio exome and whole-genome sequencing (WGS). We used a comprehensive clinical assessment, genome-wide methylation analysis (GMA), reanalysis of WGS data, and CHD7 RNA studies to discover a novel variant that causes CHD7 haploinsufficiency. The 7-year-old Hispanic male proband has typical phenotypic features of CHARGE syndrome. GMA revealed a CHD7-associated epigenetic signature. Reanalysis of the WGS data with focused bioinformatic analysis of CHD7 detected a novel, de novo 15 base pair deletion in Intron 4 of CHD7 (c.2239-20_2239-6delGTCTTGGGTTTTTGT [NM_017780.3]). Using proband RNA, we confirmed that this novel deletion causes CHD7 haploinsufficiency by disrupting the canonical 3' splice site and introducing a premature stop codon. Integrated genomic, epigenomic, and transcriptome analyses discovered a novel CHD7 variant that causes CHARGE syndrome.","journal":"American Journal of Medical Genetics Part A","year":2020,"id":74514,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":368996,"name":"Daniel Wegner","orcid":"0000-0002-1625-2830","position":1,"is_corresponding":false},{"id":391426,"name":"Alexander J. Paul","orcid":null,"position":2,"is_corresponding":false},{"id":283745,"name":"Marcia Willing","orcid":null,"position":3,"is_corresponding":false},{"id":391427,"name":"Kathleen Sisco","orcid":null,"position":4,"is_corresponding":false},{"id":390024,"name":"Matthew L. Tedder","orcid":"0000-0003-0613-6702","position":5,"is_corresponding":false},{"id":390025,"name":"Bekim Sadiković","orcid":"0000-0001-6363-0016","position":6,"is_corresponding":false},{"id":369001,"name":"Jennifer Wambach","orcid":"0000-0002-9299-0499","position":7,"is_corresponding":false},{"id":274077,"name":"Dustin Baldridge","orcid":"0000-0002-6027-6020","position":8,"is_corresponding":false},{"id":308565,"name":"F. Sessions Cole","orcid":"0000-0002-3797-9369","position":9,"is_corresponding":false},{"id":276384,"name":"Undiagnosed Diseases Network","orcid":null,"position":10,"is_corresponding":false},{"id":390023,"name":"Jorge L. Granadillo","orcid":"0000-0003-4243-204X","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T21:46:11.663457Z","pmid":"33184947","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":[]}