Statins Downregulate K6a Promoter Activity: A Possible Therapeutic Avenue for Pachyonychia Congenita

Statins downregulate K6a promoter activity: a possible therapeutic avenue for pachyonychia congenita.

Pachyonychia congenita (PC) is a keratinizing disorder predominantly caused by mutations in keratin 6a (K6a) (∼50% of cases) or K6b, K16, or K17. One means of treating PC is identification of small-molecule inhibitors of PC-related keratins. Here, we cloned the human K6a promoter, and using a cell-based reporter gene assay, a chemical library was screened for K6a inhibitors. One compound, compa...

Development of therapeutic siRNAs for pachyonychia congenita.

Pachyonychia congenita (PC) is an autosomal-dominant keratin disorder where the most painful, debilitating aspect is plantar keratoderma. PC is caused by mutations in one of four keratin genes; however, most patients carry K6a mutations. Knockout mouse studies suggest that ablation of one of the several K6 genes can be tolerated owing to compensatory expression of the others. Here, we have deve...

Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita.

The field of science and medicine has experienced a flood of data and technology associated with the human genome project. Over 10,000 human diseases have been genetically defined, but little progress has been made with respect to the clinical application of this knowledge. A notable exception to this exists for pachyonychia congenita (PC), a rare, dominant-negative keratin disorder. The establ...

Pachyonychia Congenita in a Toddler

Pachyonychia congenita: A rare genodermatosis

Pachyonychia congenita (PC) is a rare genodermatosis with only 450 cases reported since 1906. It is of two types, type I due to mutation in genes 6a and 16, and 6b and 17 in type II with an autosomal dominant inheritance in both types. A 22 yr old female patient presented in our OPD with hypertrophy of finger and toe nails, palmoplantar keratoderma, oral punctuate leukokeratosis, hyperhidrosis ...