{"doi":"10.1002/humu.24257","title":"A custom capture sequence approach for oculocutaneous albinism identifies structural variant alleles at the <i>OCA2</i> locus","abstract":"Oculocutaneous albinism (OCA) is a heritable disorder of pigment production that manifests as hypopigmentation and altered eye development. Exon sequencing of known OCA genes is unsuccessful in producing a complete molecular diagnosis for a significant number of affected individuals. We sequenced the DNA of individuals with OCA using short-read custom capture sequencing that targeted coding, intronic, and noncoding regulatory regions of known OCA genes, and genome-wide association study-associated pigmentation loci. We identified an OCA2 complex structural variant (CxSV), defined by a 143 kb inverted segment reintroduced in intron 1, upstream of the native location. The corresponding CxSV junctions were observed in 11/390 probands screened. The 143 kb CxSV presents in one family as a copy number variant duplication for the 143 kb region. In the remaining 10/11 families, the 143 kb CxSV acquired an additional 184 kb deletion across the same region, restoring exons 3-19 of OCA2 to a copy-number neutral state. Allele-associated haplotype analysis found rare SNVs rs374519281 and rs139696407 are linked with the 143 kb CxSV in both OCA2 alleles. For individuals in which customary molecular evaluation does not reveal a biallelic OCA diagnosis, we recommend preliminary screening for these haplotype-associated rare variants, followed by junction-specific validation for the OCA2 143 kb CxSV.","journal":"Human Mutation","year":2021,"id":192085,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"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":707132,"name":"Linnea Lundh","orcid":null,"position":1,"is_corresponding":false},{"id":471310,"name":"Dawn E. Watkins‐Chow","orcid":"0000-0002-4355-0868","position":2,"is_corresponding":false},{"id":471311,"name":"Laura L. Baxter","orcid":"0000-0001-7941-1088","position":3,"is_corresponding":false},{"id":81225,"name":"Erola Pairo-Castineira","orcid":"0000-0002-2423-3090","position":4,"is_corresponding":false},{"id":406002,"name":"NISC Comparative Sequencing Program","orcid":null,"position":5,"is_corresponding":false},{"id":391221,"name":"Ian J. Jackson","orcid":"0000-0001-6526-0688","position":6,"is_corresponding":false},{"id":433918,"name":"William S. Oetting","orcid":"0000-0002-1076-0711","position":7,"is_corresponding":false},{"id":232070,"name":"William J. Pavan","orcid":"0000-0001-8281-5120","position":8,"is_corresponding":false},{"id":362136,"name":"David R. Adams","orcid":"0000-0002-6660-1242","position":9,"is_corresponding":false},{"id":758566,"name":"Stacie K. Loftus","orcid":"0000-0002-1958-4689","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-18T23:49:39.281850Z","pmid":"34246199","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":[]}