Mutations of Keratin 9 in Two Families with Palmoplantar Epidermolytic Hyperkeratosis

Bonifas, Jeannette M.; Matsumura, Kunie; Chen, Marisa A; Berth‐Jones, J.; Hutchinson, P.E.; Zloczower, Michael; Fritsch, Peter; Epstein, Ervin

doi:10.1111/1523-1747.ep12395570

Cited by 64 publications

(50 citation statements)

References 23 publications

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“…In previous reports on the K9 mutation, eight types of point mutations were reported [4][5][6][7][8] as summarized in Fig. 3. (1) M156V: substitution of valine for methionine at amino acid 156 by A to G transition at nt 532 [6]; (2) N160Y: substitution of tyrosine for asparagine at amino acid 160 by the transversion of A to T at nt 544 [4]; (3) N160S: serine for asparagine at 160 by the transversion of A to G transition at nt 545 [7]; (4) N160K: lysine for asparagine at 160 by T to A transversion at nt 546 [5]; (5) R162W: tryptophan for arginine at 162 by C to T transition at nt 550 [5,7,8]; (6) R162Q: glutamine for arginine at 162 by G to A transition at nt 551 [5] (our cases have the same amino acid mutation of glutamine for arginine); (7) L167S: serine for leucine at 167 by transition of T to C at nt 566 [8]; and (8) Q171P: substitution of proline of glutamine at 171 by A to C transversion at nt 578 [6]. Thus, amino acids 156-171, which correspond to the head of the c~-helical domain of keratin intermediate filaments, may be a hot spot of mutation and the replacement of these amino acids may be crucial for keratin filament assembly and intermediate filament network formation in the cells.…”

Section: Sequence and Mutation Analysis Of K9mentioning

confidence: 99%

“…There are previous reports of *Corresponding author. Fax: (81) (75) 761-3002; E-mail : tanakat@kuhp.kyoto-u.ac.jp Abbreviations: EHPPK, epidermolytic hereditary palmoplantar keratoderma; IF, intermediate filament; K9, keratin 9; PCR, polymerase chain reaction; HA, hemagglutinin protein of influenza; K14, keratin 14; EBS, epidermolysis bullosa simplex point mutations in the K9 gene in EHPPK [4][5][6][7][8] but none showed a function assay with these mutations. Here, we provide the first demonstration that the point mutation found in a pedigree of EHPPK has a dominant-negative effect on the assembly of keratin intermediate filaments in the cells.…”

Section: Introductionmentioning

confidence: 99%

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Keratin 9 point mutation in the pedigree of epidermolytic hereditary palmoplantar keratoderma perturbs keratin intermediate filament network formation

et al. 1996

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Keratins form an intracellular keratin filament network in keratinocytes. Point mutations in the epidermal keratins could lead to the disruption of keratin filament formation, developing skin diseases such as epidermolytic hereditary palmoplantar keratoderma (EHPPK). We found a G to A transition in keratin 9 (K9) cDNA, resulting in the substitution of glutamine for arginine at 162, in all patients of a pedigree of EHPPK. Transfection into MDCK cells and DJM-1 cells revealed that the plasmid CMX vector containing normal keratin 9 cDNA showed normal keratin network formation, whereas the vector with a G to A point mutated keratin 9 cDNA showed disrupted keratin filaments with droplet formation in the cells. These results indicate that the point mutation seen in our patients had a dominant-negative effect on keratin network formation.

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Section: Sequence and Mutation Analysis Of K9mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Keratin 9 point mutation in the pedigree of epidermolytic hereditary palmoplantar keratoderma perturbs keratin intermediate filament network formation

et al. 1996

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“…Ultérieurement, de nombreuses équipes ont identifié des mutations ponctuelles et différentes au niveau du gène codant pour la kératine 9 [9,39,67,86,105,124,131,144]. La mutation du codon R 162 W apparaît comme la plus fréquente [105].…”

Section: La Kératodermie Palmo-plantaire De Vörnerunclassified

Les kératodermies palmo-plantaires héréditaires

Mokni¹,

Triki²,

Guedamsi³

et al. 2005

Med Chir Pied

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Les kératodermies palmo-plantaires (KPP) sont un groupe hétérogène de maladies cutanées, caractérisées par une hyperkératose des paumes et des plantes, parmi lesquelles on distingue trois groupes : KPP héréditaires, génodermatoses avec KPP et KPP acquises. Les KPP héré-ditaires sont classées selon le mode de transmission, l'aspect clinique et le type d'hyperkératose (diffus, focal ou ponctué), l'atteinte d'autres structures ectodermales, la présence ou l'absence de symptômes associés non ectodermaux, les données histologiques et la physiopathologie. Nous présentons un bilan des connaissances actuelles sur les principales KPP héréditaires.Abstract: Palmoplantar keratoderma (PKK) refers to a genetically heterogenous group of skin diseases characterised by hyperkeratosis of the palms and soles. They can be subdivided into three groups: hereditary PPK, genodermatosis with PPK and aquired PPK. Hereditary forms are classified on the basis of the morphology, distribution of the kyperkeratosis (diffuse, focal or punctate), associated symptoms, mode of inheritance and histopathologic findings. We report a review of the principal hereditary PPK.

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“…[11][12][13] and another patient (no. 6) had prenatal diagnoses of aOE ected foetuses (23), whereas, to our know-Skin biopsies were kept frozen at -70°C.…”

Section: Real Time Quantitative Pcr (Taqman)mentioning

confidence: 99%

Phenotypic/Genotypic Correlations in Patients with Epidermolytic Hyperkeratosis and the Effects of Retinoid Therapy on Keratin Expression

Virtanen¹

2001

Acta Dermato-Venereologica

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Dominant-negative mutations in the KRT1 and KRT10 genes cause epidermolytic hyperkeratosis, a rare form of ichthyosis sometimes associated with palmoplantar keratoderma. Although there is no permanent cure, some patients improve on retinoid therapy. More knowledge is needed, however, about the mechanism of action of retinoids and the genotypic/phenotypic correlations in this disease. Thirteen patients from 10 families with generalized disease and 2 sporadic patients with nevoid lesions were studied, probably representing most of the patients in Sweden and Norway. All patients, except one nevoid case, were known to have KRT1 or KRT10 mutations. Those with mutated keratin 1 (K1) invariably had associated keratoderma (n=6). In contrast, only 1 of 7 patients with K10 mutations had this problem (p = 0.0047). Five out of 6 patients with KRT10 mutations benefited from treatment with oral acitretin (5-25mg/day) or topical tretinoin/tazarotene, but none of the patients with KRT1 mutations derived any benefit. Quantitative analysis of K1 and K10 mRNA in skin biopsies obtained before and after retinoid therapy (n=8) showed no consistent down-regulation of mutated keratin that would explain the therapeutic outcome. Instead, the mRNA expression of K2e (a normal constituent of the upper epidermis) diminished especially in nonresponders. In contrast, K4 mRNA and protein (marker of retinoid bioactivity in normal epidermis) increased in almost all retinoid-treated patients. In conclusion, our study confirms a strong association between KRT1 mutations and palmoplantar keratoderma. Retinoid therapy is particularly effective in patients with KRT10 mutations possibly because they are less vulnerable to a down-regulation of K2e, potentially functioning as a substitute for the mutated protein in patients with KRT1 mutations.

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Mutations of Keratin 9 in Two Families with Palmoplantar Epidermolytic Hyperkeratosis

Cited by 64 publications

References 23 publications

Keratin 9 point mutation in the pedigree of epidermolytic hereditary palmoplantar keratoderma perturbs keratin intermediate filament network formation

Keratin 9 point mutation in the pedigree of epidermolytic hereditary palmoplantar keratoderma perturbs keratin intermediate filament network formation

Les kératodermies palmo-plantaires héréditaires

Phenotypic/Genotypic Correlations in Patients with Epidermolytic Hyperkeratosis and the Effects of Retinoid Therapy on Keratin Expression

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