KRT14 – Epidermolysis Bullosa Simplex 2F, with mottled pigmentation

Epidermolysis bullosa simplex 2F with mottled pigmentation (EBS-MP) is a rare autosomal dominant disorder of basal keratinocytes characterized by mechanical stress-induced blistering and reticulated hyperpigmentation. Filament defects in keratin 5/14 heterodimers underlie EBS subtypes, but the only pathogenic variant reported in EBS-MP is a KRT5 c.74C>T (p.Pro25Leu) mutation identified in two unrelated families ([PMID:8799157]).

Keratin 14 is essential for K5/K14 filament assembly, and functional studies of KRT14 mutants demonstrate dominant-negative disruption of intermediate filaments in vivo and in vitro, recapitulating classical EBS phenotypes. However, no KRT14 variants have been described in patients with mottled pigmentation, limiting direct genetic evidence for KRT14 in EBS-MP. The pathogenic mechanism in EBS involves dominant-negative perturbation of filament architecture; KRT14 functional data are concordant with this model but not specific to the mottled pigmentation subtype. Further screening of KRT14 in EBS-MP cohorts may clarify its role, but current evidence supports only a limited association. Key take-home: diagnostic testing for EBS-MP should prioritize KRT5, with KRT14 evaluation reserved for KRT5-negative cases.

References

• Proceedings of the National Academy of Sciences of the United States of America • 1996 • The genetic basis of epidermolysis bullosa simplex with mottled pigmentation PMID:8799157

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