Polymorphous presentation of subcutaneous phaeohyphomycosis: a rare occurrence

To avoid a misleading genetic diagnosis of epidermolysis bullosa Dear Editor, Zeng et al. recently reported a young female patient with epidermolysis bullosa (EB), who showed extensive epidermal exfoliation, subepidermal blisters, and erosions with dystrophy of all her nails. Based on direct sequencing and 100 reference DNAs, a heterozygous c.280G>A mutation of KRT14, which leads to a p.Ala94Thr change in the head domain of keratin 14, was concluded to be the causative mutation in the case, and the Koebner form of EB simplex was diagnosed. However, when I examined mutations for a Japanese case with EB, I noticed that this variant, 17:39742807C/T, was matched to a SNP (RefSNP ID: rs3826550) and the frequency of the minor allele was as high as 0.352 in ID: ss1692775521 of EVA_EXAC [Batch ID: The Exome Aggregation Consortium (ExAC)_0.3] or 0.73 in a report by Chamcheu et al. Therefore, it is unlikely that the SNP reported in KRT14 causes EB simplex. When histological data are limited, we often rely on genetic analysis for the differential diagnosis of EB. Indeed, the detection of such mutations in causative genes is helpful for the diagnosis of EB. However, each mutation should be carefully discriminated from simple polymorphisms for proper genetic diagnosis. Recent public human genome databases, such as ExAC, in which the sample size is as high as 60,706, providing a large human reference database, are useful to exclude common polymorphisms and to narrow down candidate mutations in the analysis of EB. We hope that the report by Zeng et al. will be revised properly by further extensive genetic analysis using whole exome sequencing.