Journal of the American Academy of Dermatology
Volume 62, Issue 1 , Pages 107-113 , January 2010

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

  • Reuven Bergman, MD

      Affiliations

    • Department of Dermatology, Rambam Medical Center, Haifa, Israel
    • Corresponding Author InformationCorrespondence to: Reuven Bergman, MD, Department of Dermatology, Rambam Medical Center, Haifa, 31096, Israel.
    • ,
  • Dov Hershkovitz, MD

      Affiliations

    • Department of Pathology, Rambam Medical Center, Haifa, Israel
    • ,
  • Dana Fuchs, MSc

      Affiliations

    • Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
    • ,
  • Margarita Indelman, MSc

      Affiliations

    • Department of Dermatology, Rambam Medical Center, Haifa, Israel
    • ,
  • Yael Gadot, MD

      Affiliations

    • Department of Dermatology, Rambam Medical Center, Haifa, Israel
    • ,
  • Eli Sprecher, MD

      Affiliations

    • Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

,Accepted 14 May 2009.

References 

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  2. Ries A, Hennies AC, Langbein L, Diqweed M, Mischke D, Drechsler M, et al. Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK). Nat Genet. 1994;2:174–179
  3. Bergman R, Khamaysi Z, Sprecher E. A unique pattern of dyskeratosis characterizes epidermolytic hyperkeratosis and epidermolytic palmoplantar keratoderma. Am J Dermatopathol. 2008;2:101–105
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  8. Wan H, Dopping-Hepenstal PJ, Gratian MJ, Stone MG, Zhu G, Purkis PE, et al. Striate palmoplantar keratoderma arising from desmoplakin and desmoglein 1 mutations is associated with contrasting perturbations of desmosomes and the keratin filament network. Br J Dermatol. 2004;150:878–891
  9. Whittock NV, Ashton GHS, Dopping-Hepenstal PJC, Gratian MJ, Keane FM, Eady RA, et al. Striate palmplantar keratoderma resulting from desmoplakin haploinsufficiency. J Invest Dermatol. 1999;6:940–946
  10. Keren H, Bergman R, Mizrachi M, Kashi Y, Sprecher E. Diffuse nonepidermolytic palmoplantar keratoderma caused by a recurrent nonsense mutation in DSG1. Arch Dermatol. 2005;5:625–628
  11. Hershkovitz D, Lugassy J, Indelman M, Bergman R, Sprecher E. Novel mutations in DSG1 causing striate palmoplantar keratoderma. Clin Exp Dermatol. 2009;34:224–228
  12. Hunt DM, Rickman L, Whittock NV, Eady RA, Simrak D, Dopping-Hepenstal PJ, et al. Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing the skin disease striate palmoplantar keratoderma. Eur J Hum Genet. 2001;3:197–203
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  14. Milingou M, Wood P, Masouye I, McLean WH, Borradori L. Focal palmoplantar keratoderma caused by an autosomal dominant inherited mutation in the desmoglein 1 gene. Dermatology. 2006;2:117–122
  15. Norgett EE, Hatsell SJ, Carvajal-Huerta L, Cabezas JC, Common J, Purkis PE, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, wooly hair and keratoderma. Hum Mol Genet. 2000;18:2761–2766
  16. Uzumcu A, Norgett EE, Dindar A, Uyguner O, Nisli K, Kayserili H, et al. Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in Naxos-like syndrome. [letter] J Med Genet. 2006;2:e5
  17. Whittock NV, Wan H, Morley SM, Garzon MC, Kristal L, Hyde P, et al. Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin underlies skin fragility/wooly hair syndrome. J Invest Dermatol. 2002;2:232–238
  18. Dusek RL, Godsel LM, Green KJ. Discriminating roles of desmosomal cadherins: beyond desmosomal adhesion. J Dermatol Sci. 2007;1:7–21
  19. McGrath JA, McMillian JR, Shemanko CS, Runswick SK, Leigh IM, Lane EB, et al. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet. 1997;2:240–244
  20. McGrath JA, Hoeger PH, Christiano AM, McMillan JR, Mellerio JE, Ashton GH, et al. Skin fragility and hypohidrotic ectodermal dysplasia resulting from ablation of plakophilin 1. Br J Dermatol. 1999;2:297–307
  21. Whittock NV, Haftek M, Angoulvant N, Wolf F, Perrot H, Eady RA, et al. Genomic amplification of the human plakophilin 1 gene and detection of a new mutation in ectodermal dysplasia/skin fragility syndrome. J Invest Dermatol. 2000;3:368–374
  22. Hamada T, South AP, Mitsuhashi Y, Kinebuchi T, Bleck O, Ashton GH, et al. Genotype-phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1. Exp Dermatol. 2002;2:107–114
  23. Sprecher E, Molho-Pessach V, Ingber A, Sagi E, Indelman M, Bergman R. Homozygous splice site mutations in PKP1 result in loss of epidermal plakophilin 1 expression and underlie ectodermal dysplasia/skin fragility syndrome in two consanguineous families. J Invest Dermatol. 2004;3:647–651
  24. Bergman R, Sprecher E. The histopathology of ectodermal dysplasia/skin fragility syndrome. Am J Dermatopathol. 2005;4:333–338
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  26. Smith FJ, Del Monaco M, Steijlen PM, Munro CS, Morvay M, Coleman CM, et al. Novel proline substitution mutations in keratin 16 in two cases of pachyonychia congenital type I. Br J Dermatol. 1999;6:1010–1016
  27. Shamsher MK, Navsaria HA, Stevens HP, Ratnavel RC, Purkis PE, Kelsell DP, et al. Novel mutations in keratin 16 gene underlie focal non-epidermolytic palmoplantar keratoderma (NEPPK) in two families. Hum Mol Genet. 1995;4:1875–1881
  28. Liao H, Sayers JM, Wilson NJ, Irvine AD, Mellerio JE, Baselga E, et al. A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita. J Dermatol Sci. 2007;48:199–205
  29. Terrinoni A, Puddu P, Didona B, De Laurenzi V, Candi E, Smith FJD. A mutation in the V1 domain of K16 is responsible for unilateral palmoplantar verrucous nevus. J Invest Dermatol. 2000;114:1136–1140

 Funding sources: None.

 Conflicts of interest: None declared.

 Reprints not available from the authors.

PII: S0190-9622(09)00614-8

doi: 10.1016/j.jaad.2009.05.016

Journal of the American Academy of Dermatology
Volume 62, Issue 1 , Pages 107-113 , January 2010

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