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The following is a summary of “Functional genotype classification groups distinguish disease severity in recessive dystrophic epidermolysis bullosa,” published in the January 2025 issue of Dermatology by Pathmarajah et al.
Recessive dystrophic epidermolysis bullosa (RDEB) was identified as a genetic disorder caused by pathogenic variants in the COL7A1 gene.
Researchers conducted a retrospective study to examine the association between various categories of COL7A1 variants and clinical disease severity in 236 patients with RDEB in North America.
They used published reports and in-silico predictions to evaluate the effect of pathogenic COL7A1 variants on type VII collagen (C7) function. Impact was categorized into 3 groups: low impact (splice B/missense, missense/missense), medium impact [premature termination codon (PTC)/splice B, splice A/splice B, PTC/missense, splice A/missense, splice B/splice B], and high impact (PTC/PTC, PTC/splice A, splice A/splice A). Splice A variants were expected to cause downstream PTCs, while splice B variants resulted in in-frame exon skipping, which is less deleterious.
The results showed a significant association between functional impact severity and clinical factors, including gastrostomy tube placement, esophageal dilation, hand surgery, anemia, renal disease, chronic wounds, diffuse skin involvement, and squamous cell carcinoma. The odds of death were 3.25 times higher (1.24-8.50, P =0.02) in the high-impact group compared to the medium-impact group. Patients in the high-impact group experienced worse clinical outcomes.
Investigators concluded that patients based on the predicted functional impact of COL7A1 gene mutations might aid in risk stratification and potentially improve the management of RDEB.
Source: academic.oup.com/bjd/advance-article-abstract/doi/10.1093/bjd/ljaf015/7951002
