{"doi":"10.1093/bjd/ljaf015","title":"Functional genotype classification groups distinguish disease severity in recessive dystrophic epidermolysis bullosa","abstract":"BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder caused by pathogenic variants in COL7A1. OBJECTIVES: To determine the association between different COL7A1 variants and clinical disease severity in 236 North American patients with RDEB. METHODS: Published reports or in silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function. Three impact categories were postulated: genotypes that would be likely to cause a low impact on C7 function (splice B/missense, missense/missense); a medium impact [premature termination codon (PTC)/splice B, splice A/splice B, PTC/missense, splice A/missense, splice B/splice B]; and a high impact (PTC/PTC, PTC/splice A, splice A/splice A). Splice A variants are predicted to cause downstream PTCs, while splice B variants cause in-frame exon skipping and are therefore less deleterious. RESULTS: The severity of functional impact was significantly associated with a history of gastrostomy tube placement, oesophageal dilation, hand surgery, anaemia, renal disease, chronic wounds, diffuse skin involvement and a history of squamous cell carcinoma. The odds of death were 3.5 time higher in the high-impact vs. medium-impact group (95% confidence interval 1.24-8.50; P = 0.02). Patients in the high-impact group had worse clinical outcomes. CONCLUSIONS: Functional genotype categories are a feasible approach to risk-stratify patients based on predicted C7 function.","journal":"British Journal of Dermatology","year":2025,"id":525145,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1150847,"name":"Edward Eid","orcid":"0000-0002-9355-2474","position":1,"is_corresponding":false},{"id":1399337,"name":"Jaron Nazaroff","orcid":"0000-0002-4267-6776","position":2,"is_corresponding":false},{"id":1399338,"name":"Jodi So","orcid":"0000-0002-4395-2752","position":3,"is_corresponding":false},{"id":33997,"name":"Vaishali Mittal","orcid":"0009-0002-9486-889X","position":4,"is_corresponding":false},{"id":1399964,"name":"Nicki Harris","orcid":null,"position":5,"is_corresponding":false},{"id":693863,"name":"Shufeng Li","orcid":"0000-0001-6031-0893","position":6,"is_corresponding":false},{"id":594755,"name":"Anne W. Lucky","orcid":"0000-0002-6115-7584","position":7,"is_corresponding":false},{"id":492155,"name":"Emily S. Gorell","orcid":"0000-0002-2813-3089","position":8,"is_corresponding":false},{"id":978578,"name":"Kathleen Peoples","orcid":null,"position":9,"is_corresponding":false},{"id":1104833,"name":"Elena Pope","orcid":"0000-0002-2136-5661","position":10,"is_corresponding":false},{"id":334876,"name":"Irene Lara‐Corrales","orcid":"0000-0002-3210-3413","position":11,"is_corresponding":false},{"id":388127,"name":"Amy S. Paller","orcid":"0000-0001-6187-6549","position":12,"is_corresponding":false},{"id":391223,"name":"Karen Wiss","orcid":"0000-0002-7753-6503","position":13,"is_corresponding":false},{"id":978215,"name":"Marissa J. Perman","orcid":"0000-0002-6780-8157","position":14,"is_corresponding":false},{"id":978213,"name":"Lawrence F. Eichenfield","orcid":"0000-0002-2760-0474","position":15,"is_corresponding":false},{"id":642612,"name":"Moise L. Levy","orcid":"0000-0002-8605-0935","position":16,"is_corresponding":false},{"id":978214,"name":"Kimberly D. Morel","orcid":"0000-0003-0646-8192","position":17,"is_corresponding":false},{"id":808771,"name":"María Teresa García‐Romero","orcid":"0000-0002-1408-8109","position":18,"is_corresponding":false},{"id":1137265,"name":"Catherine McCuaïg","orcid":"0000-0003-0792-6247","position":19,"is_corresponding":false},{"id":1399965,"name":"Mélissa Saber","orcid":null,"position":20,"is_corresponding":false},{"id":45766,"name":"M. Peter Marinkovich","orcid":"0000-0001-5528-8046","position":21,"is_corresponding":false},{"id":317845,"name":"Anthony E. Oro","orcid":"0000-0002-6261-138X","position":22,"is_corresponding":false},{"id":876134,"name":"Anna L. Bruckner","orcid":"0000-0002-2035-4127","position":23,"is_corresponding":false},{"id":30252,"name":"Jean Y. Tang","orcid":"0000-0002-5510-6502","position":24,"is_corresponding":false},{"id":1322340,"name":"Pirunthan Pathmarajah","orcid":"0000-0002-9395-5935","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:50:16.562292Z","pmid":"39790012","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":[]}