Homozygous Dominant Missense Mutation in Keratin 17 Leads to Alopecia in Addition to Severe Pachyonychia Congenita

The document discussed the diverse and significant roles of human keratins, which are intermediate filament proteins crucial for the mechanical stability and integrity of epithelial cells and tissues. It highlighted that humans have 54 functional keratin genes, with about half being specific to hair follicles. Keratins not only provide structural support but also participate in regulatory functions such as stress protection, wound healing, and apoptosis. The article summarized the distribution and functional significance of keratins in relation to transgenic mouse models and human hereditary keratin diseases. Additionally, certain keratins, like K5, K7, K8/K18, K19, and K20, were noted for their importance in the immunohistochemical diagnosis of carcinomas, particularly in identifying unclear metastases and aiding in tumor classification and subtyping. The document suggested that future research could expand the clinical applications of keratins.

The study on Keratin 17 (K17) null mice revealed that these mice developed severe alopecia within the first week after birth, linked to hair fragility, changes in follicular histology, and apoptosis in matrix cells. These effects were not fully penetrant and began to normalize with the first postnatal cycle. The absence of a hair phenotype was associated with genetic strain-dependent compensation by related keratins, such as K16. The research highlighted the essential role of K17 in maintaining the structural integrity of initial hair and the survival of hair-producing cells. The study also suggested that clinical heterogeneity in conditions like pachyonychia congenita or steatocystoma multiplex could be due to cell type-specific, genetically determined compensation by related keratins.