Focal palmoplantar keratoderma (palmoplantar keratoderma Focal) - Genes KRT6C or KRT16.

Focal palmoplantar keratoderma is a skin condition characterized by the development of painful blisters and callouses on the soles and, less frequently, in the palms. In general, skin anomalies begin in childhood and mainly affect areas presenting trauma or friction. Blisters and calluses on the feet can cause pain and difficulty walking. Some people with focal palmoplantar keratoderma also have very slight alterations of the fingernails and toenails.

Palmoplantar keratoderma focal may be due to mutations in the gene KRT6C, located on the long arm of chromosome 12 (12q13.13) or KRT16 gene, located on the long arm of chromosome 17 (17q21.2). These genes encode 6c and keratin 16. keratin proteins Keratins are fibrous proteins that act together to provide strength and resilience of the tissues that make up the skin, hair and nails.

They have been identified, at least, three mutations in the gene KRT6C and 4 KRT16 genetic mutations responsible focal palmoplantar keratoderma. One of the mutations associated with the gene KRT6C change a single amino acid in the protein keratin 6c. Specifically, this mutation replaces the amino acid glutamic acid for lysine at amino acid position 472 of protein (Glu472Lys or E472K). Other genetic mutations KRT6C eliminate one or more amino acids of the protein keratin 6c. Meanwhile, the mutations identified in the gene KRT16, change amino acids in the protein keratin 16 or remove a large region of the protein keratin 16. All mutations identified in the gene KRT6C and the gene KRT16 alter the structure of keratin 6c and 16, and interfere with the overall network of keratin intermediate filaments. The skin cells with defective keratin are fragile and prone to damage, so the skin becomes less resistant to friction and minor trauma. The soles have a more significant friction compared to many other parts of the body, which may help explain why the blisters and corns occur mainly in this area in people with focal palmoplantar keratoderma.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In some cases, an affected person inherits the mutation from an affected parent. Other affected individuals have no family history of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with focal palmoplantar keratoderma, by complete PCR amplification of the exons of KRT6C and KRT16, respectively, genes and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).