Mutations in Keratin K9 in Kindreds with Epidermolytic Palmoplantar Keratoderma and Epidemiology in Northern Ireland

Abstract

Epidermolytic palmoplantar keratoderma (EPPK, MIM #144200) is an autosomal dominant disorder in which hyperkeratosis confined to the palms and soles is characterized histologically by cytolysis of suprabasal keratinocytes. Mutations in the keratin 9 gene (KRT9), a type 1 keratin expressed exclusively in the suprabasal keratinocytes of palmoplantar epidermis, have previously been demonstrated in this disorder. Here, we have studied four Northern Irish kindreds presenting with EPPK. By direct sequencing of polymerase chain reaction products, heterozygous missense mutations in exon 1 of KRT9 were detected in all the families. These included a novel mutation M156T; as well as M156V in two kindreds; and R162Q in the remaining family. All mutations were confirmed by reverse strand sequencing and restriction enzyme analysis. The point prevalence of EPPK in Northern Ireland was found to be 4.4 per 100,000. To date, all reported EPPK mutations occur in the helix initiation motif at the start of the central coiled-coil rod domain of K9.

Keratin gene mutations in disorders of human skin and its appendages

“…Nevertheless, other not yet identified genetic or epigenetic modifiers and environmental factors, such as patient lifestyle and climate condition, clearly influence the phenotypic expression as different subtypes of EBS have been associated with the same mutation in several instances [35–37]. …”

Citoqueratinas

“…Nos pacientes com defeito da CQ 10, talvez a CQ 9, presente no estrato lúcido, compense o defeito da CQ 10, já que são do mesmo grupo de CQ ácidas, 26 se bem que já foram descritas mutações da CQ 10 com acometimento palmoplantar. 27 As mutações da CQ 9, já que é encontrada na epiderme palmoplantar, acompanham-se de degeneração restrita a essa área, típica da queratodermia palmoplantar epidermolítica; [28][29][30] 19,20 the first illness in which the mutation of a CK. 21 was demonstrated.…”

Cloning of multiple keratin 16 genes facilitates prenatal diagnosis of pachyonychia congenita type 1

“…However, we recently reported a point prevalence in Northern Ireland of 4.4 per 100 000 for a closely related keratin disorder, epidermolytic palmoplantar keratoderma (EPPK), caused by mutations in K9 (Covello et al, 1998a). Only one keratin gene is involved in EPPK, whereas four are known to produce PC and/or FNEPPK .…”