2.1. Pachyonychia Congenita

At least four mutations in the KRT6B gene have been identified in people with pachyonychia congenita, a rare condition that primarily affects the nails and skin. In most cases, this condition becomes apparent within the first few months of life. These mutations either change single protein building blocks (amino acids) in keratin 6b or delete a small number of amino acids from the protein.

The KRT6B gene mutations responsible for pachyonychia congenita change the structure of keratin 6b, preventing it from interacting effectively with keratin 17 and interfering with the assembly of the keratin intermediate filament network. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Even normal activities such as walking can cause skin cells to break down, resulting in the formation of painful blisters and calluses. In the sebaceous glands, abnormal keratin filaments lead to the development of sebum-filled cysts called steatocystomas. Defective keratin 6b also disrupts the growth and function of other tissues, such as the hair follicles and nails, which explains why the signs and symptoms of pachyonychia congenita can also affect these other parts of the body.