Keratin gene mutations in disorders of human skin and its appendages

The study examined keratin expression in the nail unit using antikeratin monoclonal antibodies, revealing distinct patterns of differentiation. The nail matrix uniquely expressed the acidic hair-type keratin Ha1, alongside epidermal keratins K1 and K10, with occasional K17 at the matrix apex. K6 and K16 were present at the ventral aspect of the proximal nail fold. The nail bed lacked Ha1 and markers of cornified and mucosal differentiation but contained K6, K16, and K17, indicating minimal differentiation due to the nail's properties. In the digit pulp, K6, K16, and K17 were found in limited amounts, possibly linked to the eccrine duct's epidermal component. Simple epithelial keratins K7, K8, and K18 were present in younger individuals, mainly in epibasal cells and putative Merkel cells.

Monilethrix, a rare autosomal dominant hair disorder, was studied in 12 families and sporadic cases, focusing on mutations in the helix termination motif of keratin hHb6. Mutations were found in 6 families, with 4 families exhibiting known mutations (Glu413Lys and Glu413Asp) and 2 families showing a novel mutation (Glu402Lys). The study found no clear link between mutation type and disease severity, as heterozygous family members displayed varying symptoms, while homozygous individuals in a consanguineous family were more severely affected. This suggested that other genetic or environmental factors might influence the condition.

The study identified that mutations in the keratin 17 (K17) gene were responsible for both pachyonychia congenita type 2 (PC-2) and steatocystoma multiplex, with the phenotypic outcome being independent of the specific mutation. Three unrelated families with K17 mutations were examined, revealing that two families shared the same missense mutation (R94C) but exhibited different phenotypes: one with classical PC-2 features and the other with steatocystoma multiplex. A third family with PC-2 had a different mutation (N92S). The research highlighted that K17 mutations were a common underlying cause for both conditions, expanding the known distinct mutations in K17 to 11.