Functional genotype-phenotype associations in recessive dystrophic epidermolysis bullosa - 20/08/24
Abstract |
Background |
Genotype-phenotype associations in recessive dystrophic epidermolysis bullosa (RDEB) have been difficult to elucidate.
Objective |
To investigate RDEB genotype-phenotype associations and explore a functional approach to genotype classification.
Methods |
Clinical examination and genetic testing of RDEB subjects, including assessment of clinical disease by RDEB subtype and extent of blistering. Genotypes were evaluated according to each variant's effect on type VII collagen function per updated literature and subsequently categorized by degree of impact on VII collagen function as low-impact (splice/missense, missense/missense), medium-impact (premature termination codon [PTC]/missense, splice/splice), and high-impact (PTC/PTC, PTC/splice). Genotype-phenotype associations were investigated using Kruskal-Wallis and Fisher's exact tests, and age-adjusted regressions.
Results |
Eighty-three participants were included. High-impact variants were associated with worse RDEB subtype and clinical disease, including increased prevalence of generalized blistering (55.6% for low-impact vs 72.7% medium-impact vs 90.4% high-impact variants, P = .002). In age-adjusted regressions, participants with high-impact variants had 40.8-fold greater odds of squamous cell carcinoma compared to low-impact variants (P = .02), and 5.7-fold greater odds of death compared to medium-impact variants (P = .05).
Limitations |
Cross-sectional design.
Conclusion |
Functional genotype categories may stratify RDEB severity; high-impact variants correlated with worse clinical outcomes. Further validation in larger cohorts is needed.
Il testo completo di questo articolo è disponibile in PDF.Key words : epidermolysis bullosa, genetic diseases, genodermatoses, genotype-phenotype associations, recessive dystrophic epidermolysis bullosa
Abbreviations used : AF, BMI, C7, CI, pOR, PTC, RDEB, SCC
Mappa
| Funding sources: Epidermolysis Bullosa Medical Research Foundation (Dr Tang, Dr Marinkovich), Epidermolysis Bullosa Research Partnership (Dr Tang, Dr Marinkovich), Office of Research and Development, Palo Alto Veterans Affairs Medical Center (MPM). |
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| Patient consent: Consent for the publication of recognizable patient photographs or other identifiable material was obtained by the authors and included at the time of article submission to the journal stating that all patients gave consent with the understanding that this information may be publicly available. |
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| IRB approval status: This study was approved by the Stanford Institutional Review Board (IRB #17158). |
Vol 91 - N° 3
P. 448-456 - settembre 2024 Ritorno al numero
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