1/7. An asparagine to threonine substitution in the 1A domain of keratin 1: a novel mutation that causes epidermolytic hyperkeratosis.Epidermolytic hyperkeratosis (EHK) is a congenital, autosomal dominant disorder of cornification characterized by hyperkeratosis and blister formation. The clinical manifestations are heterogeneous, with respect to the extent of body surface involvement, palmar and plantar hyperkeratosis and the presence of erythroderma. Point mutations in the genes encoding the suprabasal-specific keratins, keratins 1 and 10 have been identified in EHK patients. The inappropriate amino acid substitutions cause a collapse of the keratin filament network, resulting in cytolysis of the involved keratinocytes. We report a severe case of EHK with a single base pair mutation that causes a threonine for asparagine substitution in residue 8 (N8T) of the 1A region of the keratin 1 protein. This is the region involved in molecular overlaps between neighboring keratin heterodimers. These findings suggest that even conservative amino acid substitutions in overlap regions can cause tonofilament clumping.- - - - - - - - - - ranking = 1keywords = palm (Clic here for more details about this article) |
2/7. Epidermolytic hyperkeratosis with polycyclic psoriasiform plaques resulting from a mutation in the keratin 1 gene.Epidermolytic hyperkeratosis (EHK) is a genodermatosis caused by mutations in either the keratin 1 (K1) or keratin 10 (K10) genes, and characterized by erythroderma and blistering at birth, with development of a ribbed, ichthyotic hyperkeratosis and palmoplantar keratoderma. A wide variety of mutations within the highly conserved helix termination motifs of the central rod domains of the K1 or K10 genes correlate with the highly variable phenotypic severity observed in EHK. We report a unique EHK-like phenotype exhibiting autosomal dominant inheritance with variable expressivity in four affected individuals in a single family. Clinically, affected individuals manifest transient blistering at birth followed by chronic diffuse palmoplantar keratoderma without transgradiens. Intermittent flares of non-migratory polycylic erythematous psoriasiform plaques which worsen and abate in severity were present in all affected individuals, but showed immense individual variation in both severity and duration, ranging from weeks to months. Histopathologic examination of the psoriasiform plaques demonstrated the characteristic features of EHK. Sequencing of the K1 gene in affected family members revealed a heterozygous A-to-T transversion at nucleotide 1435 within exon 7, converting isoleucine (ATT) to phenylalanine (TTT), (I479F). The mutation resides within the highly conserved helix termination motif of the helix 2B segment of the K1 gene. This unique clinical phenotype and the associated K1 mutation have not been previously described, and it is referred to here as EHK with polycyclic, psoriasiform plaques (EHK/PPP).- - - - - - - - - - ranking = 2keywords = palm (Clic here for more details about this article) |
3/7. Phenotypic heterogeneity in bullous congenital ichthyosiform erythroderma: possible somatic mosaicism for keratin gene mutation in the mildly affected mother of the proband.BACKGROUND: Bullous congenital ichthyosiform erythroderma (BCIE) shows phenotypic variability. An epidermal nevus may represent somatic mosaicism for keratin gene mutation, which produces generalized BCIE in the next generation. This fact provides evidence that a postzygotic mutation can be passed on to the next generation in BCIE. We hypothesized that the same phenomenon occurred in a family with BCIE whose phenotypes were extremely different. OBSERVATIONS: We studied a 19-year-old boy with severe ichthyosiform erythroderma and prominent palmoplantar hyperkeratosis with digital contracture. In contrast, the proband's mother exhibited only mild ichthyosiform skin, granular verrucous lesions, and less severe streaky palmoplantar hyperkeratosis. mutation analysis in the proband showed a keratin K1 mutation (N187S, ie, an A-to-G transition at the second position of codon 187, resulting in an asparagine-to-serine substitution). In the mother, the same keratin gene mutation was recognized, but only faintly in the leukocyte dna, indicating that the amount of the mutated allele in leukocyte dna was very low compared with that from the proband. CONCLUSIONS: We speculate that the mildly affected mother showed keratin 1 gene mosaicism, and that the BCIE phenotype had been transmitted in a severe form through a mechanism that passes the keratin gene mutation to the next generation. These results suggest that mild forms of BCIE may actually represent extensive epidermal nevi/keratin gene mosaicism.- - - - - - - - - - ranking = 2keywords = palm (Clic here for more details about this article) |
4/7. A keratin 10 gene mutation (Arg156Cys) in a Japanese patient with bullous congenital ichthyosiform erythroderma.We described a 19-year old Japanese female with bullous congenital ichthyosiform erythroderma (BCIE) and examined the keratin gene mutation. physical examination disclosed generalized erythema, ichthyosiform skin with scales, and erosions without palmoplantar keratoderma. Histological examination revealed hyperkeratosis with vacuolar degeneration in the granular layer of the epidermis. sequence analysis demonstrated a C to G transition at the first position of codon 156 in the keratin 10 gene. The amino acid at codon 156 was deduced to have changed from arginine to cystine. Substitution from arginine to cysteine at codon 156 of the K 10 gene is assumed to be fatal for keratin filament assembly regardless of racial or ethnic difference.- - - - - - - - - - ranking = 1keywords = palm (Clic here for more details about this article) |
5/7. Annular epidermolytic ichthyosis.A 21-year-old woman presented to the Charles C. Harris skin and Cancer Pavilion with a life-long history of palmoplantar keratoderma that was accompanied by episodic flares of polycyclic psoriasiform patches diffusely over the rest of her body. A biopsy specimen of a representative skin lesion showed epidermolytic hyperkeratosis. The particular phenotype that this patient exhibited has been reported in only seven families previously in the literature. Mutations in keratin 1 and 10 have been identified in these patients and are similar to those mutations in patients with classic epidermolytic hyperkeratosis.- - - - - - - - - - ranking = 1keywords = palm (Clic here for more details about this article) |
6/7. Epidermolytic hyperkeratosis type PS-1 caused by aberrant splicing of KRT1.Mutations in the keratin 1 (KRT1) gene underlie epidermolytic hyperkeratosis (EHK). This autosomal dominant disorder is characterized by phenotypic heterogeneity. In the present study, we assessed a 33-year-old individual presenting with severe palmoplantar keratoderma and histopathological findings suggestive of EHK. We analysed genomic dna extracted from the patient's blood lymphocytes for pathogenic mutations in KRT1. A heterozygous 4-bp deletion was identified in intron 1 of the gene (591 3_ 6delGAGT), suggesting the possibility that it may interfere with the normal splicing of intron 1. We detected a 66-bp deletion in KRT1 mRNA extracted from the patient's skin, predicted to result in the translation of a mutant KRT1 lacking 22 amino acids, including the conserved helix initiation motif. The identification of this unusual and novel mutation underscores the diagnostic importance of sequence analysis of keratin gene noncoding regions.- - - - - - - - - - ranking = 1keywords = palm (Clic here for more details about this article) |
7/7. A case of bullous congenital ichthyosiform erythroderma (BCIE) caused by a mutation in the 1A helix initiation motif of keratin 1.Bullous congenital ichthyosiform erythroderma (BCIE) is an autosomally dominant inherited disorder characterized by erythematous, erosive, and bullous skin lesions over the entire body at birth and abnormal hyperkeratosis on the palmoplantar sufaces as the patient grows older. BCIE is caused by a mutation in the keratin 1 (K1) and/or keratin 10 (K10) genes, and most pathogenic mutations are found within the helix initiation and termination motifs of the central helical rod domain (K1 and K10) or the upstream H1 homology domain (K10). In addition to inherited cases, sporadic cases due to a new mutation account for approximately half the total cases of BCIE. We report herein a typical sporadic case of BCIE with erythroderma, erosion, and blisters on the entire body surface at birth and palmoplantar and flexuaral areas of hyperkeratosis in the later stage. We found in this case a novel mutation, 559C to T, at amino acid position 187, which resulted in a leucine to phenylalanine substitution within the helix initiation motif of K1.- - - - - - - - - - ranking = 2keywords = palm (Clic here for more details about this article) |