A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita

A Missense Mutation within the Helix Initiation Motif of the Keratin K71 Gene Underlies Autosomal Dominant Woolly Hair/Hypotrichosis

“…Phe141 (amino-acid position 12 in the HIM) is fully conserved among all human type II keratins (Figure 3b). Furthermore, substitutions at amino-acid position 12 in the HIM of other type II keratins underlie several AD genodermatoses in humans (Stephens et al, 1997;Smith et al, 1999;Terrinoni et al, 2001;Virtanen et al, 2001;Liao et al, 2007) (Supplementary Table S1 online). Of these, substitutions from Phe to Cys at this amino-acid position have been found in K1 and K6A proteins as pathogenic mutations for epidermolytic hyperkeratosis and pachyonychia congenita type 1, respectively (Virtanen et al, 2001;Liao et al, 2007) (Supplementary Table S1 online).…”

“…Furthermore, substitutions at amino-acid position 12 in the HIM of other type II keratins underlie several AD genodermatoses in humans (Stephens et al, 1997;Smith et al, 1999;Terrinoni et al, 2001;Virtanen et al, 2001;Liao et al, 2007) (Supplementary Table S1 online). Of these, substitutions from Phe to Cys at this amino-acid position have been found in K1 and K6A proteins as pathogenic mutations for epidermolytic hyperkeratosis and pachyonychia congenita type 1, respectively (Virtanen et al, 2001;Liao et al, 2007) (Supplementary Table S1 online). In addition, all dominant mutations in the KRT71 gene responsible for wavy coat phenotype in mice have been identified in either the HIM or HTM of K71 protein (Kikkawa et al, 2003;Runkel et al, 2006;Shimomura et al, 2010b) (Figure 3a).…”

Steatocystoma multiplex

“…Besides many other epithelial structures, keratin 17 is expressed on the pilosebaceous units. Mutation in kereatin 17 is also associated with pachyonychia congenita type 2 4. Steatocystoma simplex is the sporadic solitary tumour counterpart to steatocystoma multiplex.…”

Disadhesion of epidermal keratinocytes: A histologic clue to palmoplantar keratodermas caused by DSG1 mutations

“…27 Other authors have also recognized a focal nonepidermolytic form of PPK associated with KRT16 mutations, but without other clinical signs of pachyonychia congenita type I. 28 Terrinoni et al 29 studied a patient who exhibited a localized thickening of the skin in parts of the right palm and right sole, following Blaschko lines. The keratin 16 complementary DNA sequence from the lesional epidermis demonstrated a heterozygous 12 base pair deletion, predicted to delete 4 amino acids, and proved to be a postzygotic mutation.…”