Mutations in the keratin 9 gene in Pakistani families with epidermolytic palmoplantar keratoderma

Abstract

Background-Keratins are heteropolymeric proteins that form the intermediate filament cytoskeleton in epithelial cells. The common basic structure of all keratins is organized in a central α-helical rod domain flanked by nonhelical, variable head and tail regions. Most mutations in keratins are found in the central α-helical rod domain. Keratin 9 (K9) is expressed only in the suprabasal layers of palmoplantar epidermis. Mutations in the keratin 9 gene (KRT9) have been shown to cause epidermolytic palmoplantar keratoderma (EPPK; OMIM 144200), an autosomal dominant genodermatosis characterized clinically by diffuse hyperkeratosis limited to palms and soles and histologically by epidermolysis in suprabasal layers of the epidermis.

The Most Common Mutation of KRT9, c.C487T (p.R163W), in Epidermolytic Palmoplantar Keratoderma in Two Large Chinese Pedigrees

“…Mutation screening was carried out in all members of both families as previously reported (Zhang et al, 2005; Shimomura et al, 2010). Using standard protocols, genomic DNA was extracted from the peripheral blood of all members of these two families and 100 unrelated healthy controls.…”

“…EPPK has been attributed to mutations of type I keratin gene clusters which are located at chromosome 17q21 (Reis et al, 1994). Mutations responsible for EPPK have been mainly demonstrated in the Keratin 9 gene ( KRT9 ), which is expressed exclusively in the suprabasal keratinocytes of the palmoplantar epidermis, although there are a few reports on KRT1 mutations dispersed throughout the gene (Reis et al, 1994; Rothnagel et al, 1995; Terron‐Kwiatkowski et al, 2004, 2006; Zhang et al, 2005; Feng et al, 2008; Shimomura et al, 2010; Du et al, 2011; Umegaki et al, 2011). The majority of KRT9 mutations are located in the first exon, which encodes a highly conserved coiled segment of the α‐helical rod domain; these mutations generally affect the formation of intermediate filaments and keratin heterodimerization (Reis et al, 1994).…”

Identification of a Novel Keratin 9 Missense Mutation in a Chinese Family with Epidermolytic Palmoplantar Keratoderma

“…4). All the patients suffered from diffuse palmar and plantar hyperkeratosis [9, 10, 42, 45, 54, 55]. Camptodactyly [9], hyperhidrosis [9, 55], and knuckle pads [9, 10, 55], were observed in one, two, and three families, respectively.…”

“…Among the seven KRT9 gene mutations identified in the 2B rod domain (including our mutation) [9, 10, 42, 45, 54, 55], five of them are closely distributed, ranging from p.Tyr454 to p.Leu458 [9, 42, 45, 54] (Fig. 4).…”

A recurrent p.M157R mutation of keratin 9 gene in a Chinese family with epidermolytic palmoplantar keratoderma and literature review

“…in 2008 . At the same codon, two mutations (c.470T>A and c.470T>C), which transformed methionine into lysine and threonine, respectively, has also been reported . Studies have shown that the initiative gene sequence of the coiled 1A region was confirmed by the first 15 highly conserved amino acids of 1A.…”