Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational event

Abstract

Epidermolytic hyperkeratosis is an unusual type of ichthyosis. This inherited keratinization disorder is characterized clinically by erythema, blistering, and peeling shortly after birth. It may resolve and be replaced with thick scaling. It can lead to life-threatening complications, such as sepsis. Histologically, there is a hyperkeratosis and vacuolar degeneration. Genetically, this is an autosomal dominant disease with complete penetrance; however, 50% are spontaneous mutations. The clinical phenotype is a result of alterations in the gene(s) for keratin 1 and /or 10. We review this disorder and its therapy, which is mainly symptomatic with emollients and retinoids.

Blood Gene Expression Profiling of Breast Cancer Survivors Experiencing Fibrosis

“…Substantial differences in blood gene expression were observed between the breast cancer survivors with and without fibrosis, indicating that although fibrosis is a local effect its development is related to systemic gene expression changes identifiable in blood cells. Keratin 1 (KRT1) is a type II keratin that together with keratins type I forms intermediate filaments, providing structural stability to keratinocytes, and mutations in these genes are the cause of epidermolytic hyperkeratosis, a disease characterized by skin cell collapse and clinical blistering (21). KRT1 was identified as upregulated in the fibrosis group and was also the only core gene in several gene sets, such as ''acute inflammatory response.''…”

Ichthyosis bullosa of Siemens

“…There was overlying basket weave hyperkeratosis, psoriasiform epidermal granules, and acantholysis. 1 Electron microscopy reveals a disrupted keratin filament network and clumped keratin filaments in the granular and in the spinous cells. 1 Immunofluorescence labelling with specific anti-keratin antibodies shows the keratin expressed in different epidermal layers.…”

“…1 It is a hyperkeratotic and blistering condition caused by a variety of mutations in the keratin 1 and 10 genes. It is autosomal dominant; however, 50% of cases may be sporadic due to spontaneous mutations.…”

Recombination as a mechanism for sporadic mutation in the surfactant protein‐C gene

“…Further studies may help to elucidate whether mitosis associated mutation could contribute to other diseases with high sporadic mutation rates, including Tuberous Sclerosis Complex (autosomal dominant with mutation rate approximately 2/3) 31 , Multiple Endocrine Neoplasia Type 2B (autosomal dominant, 50% sporadic mutations) 32 , Cornelia de Lange syndrome (autosomal dominant, 99% sporadic mutations) 33 , and epidermolytic hyperkeratosis (autosomal dominant, 50% sporadic) 34 . Better understanding of the mechanisms of mutation may aid in diagnosis of patients with previously negative screening results and will allow for better prospective guidance and reproductive counseling for affected families.…”