Bullous diseases caused by KRT1 gene mutations: from epidermolytic hyperkeratosis to a novel variant of epidermolysis bullosa simplex

Abstract

Introduction: Mutations in the KRT1 gene encoding keratin 1 cause epidermolytic hyperkeratosis characterized by blistering in the neonatal period followed by ichthyotic hyperkeratosis in childhood and adolescent life. We observed a spectrum of clinical manifestations of blistering disorders caused by different mutations in the same KRT1 gene. Aim: To analyse the phenotypic spectrum of blistering disorders caused by the KRT1 mutations. Material and methods: Four patients with an epidermal barrier defect manifesting as blistering with the KRT1 mutations were included to the study. The clinical course of the disease was analysed, histology, immunofluorescence and electron microscopic examinations were performed.Results: An adult patient with severe ichthyosis with p.Asn188Lys mutation in exon 1 of KRT1 who occasionally develops blisters in adolescence represents epidermolytic hyperkeratosis, a newborn child who died 4 days after birth due to disruption of the epidermal barrier (extensive blister and erosions) with mutation p.Ser193Pro in the KTR1 gene and two adult sisters harbouring heterozygous mutation c.591+1A>G in the KRT1 gene who present superficial blisters induced by mild trauma from the birth up to adolescent life without ichthyosis suggesting the diagnosis of epidermolysis bullosa simplex. Histopathology in all adult patients showed cytoplasm disruption in keratinocytes of the stratum spinosum with keratohyalin granule-like structures and, on the ultrastructural level, the presence of keratin clumping confirming the pathology of keratin intermediate filaments.Conclusions: This study extends the knowledge of the clinical spectrum for the KRT1 gene mutations. This is the first description of familial dominant epidermolysis bullosa simplex linked to the KRT1 mutation.

Identification of Critical Genes for Ovine Horn Development Based on Transcriptome during the Embryonic Period

“…Additionally, our study provides some possible candidate genes for horn development, including the KRT10 , KRT1, FMOD , free fatty acid receptor 4 ( FFAR4 ), serine protease 22 ( PRSS22 ), signal peptide, CUB domain, and EGF-like domain containing 2 ( SCUBE2 ), extracellular matrix protein 1 ( ECM1 ), and keratin 24 ( KRT24) genes. The genes KRT10 and KRT1 are expressed in keratinocytes during early differentiation [ 38 ], and their mutations cause epidermolytic hyperkeratosis [ 39 , 40 , 41 , 42 ]. In this study, KRT1 (FPKM = 3399) and KRT10 (FPKM = 2037) were found to be highly expressed in the horn buds, implying that KRT1 and KRT10 may regulate the keratinization of horn buds.…”