Potential di-genic contribution to guttate leukoderma as the predominant feature of epidermolysis bullosa simplex

Tamar Koren, Fadia Zagairy, Yasmin Tatour, Hila Belhanes-Peled, Morad Khayat, Judit Krausz, Nada Danial-Farran, Michael Ziv, Eran Cohen-Barak

Research output: Contribution to journalArticlepeer-review


Inherited epidermolysis bullosa (EB) simplex is a heterogeneous group of skin fragility disorders caused by mutations in genes encoding cell-cell or cell-matrix adhesion proteins. A recently identified, rare subtype of EB simplex is due to bi-allelic mutations in the EXPH5 gene, which encodes exophilin5, an effector protein of the Rab27B GTPase involved in intracellular vesicle trafficking and exosome secretion. The EXPH5 EB subtype is characterized by early-onset skin blisters and scars, mainly on extremities, and varying degrees of pigmentary alterations. Here, we present a 31-year-old female with diffuse guttate hypopigmentation on the trunk and extremities since early childhood, with no apparent blisters or scars. We employed whole exome sequencing of germline DNA extracted from the patient's leukocytes to determine the genetic aetiology of the phenotype. A novel homozygous variant in EXPH5, c.1153C>T causing a premature stop codon at amino acid Glutamine 385, was identified. Histologic examination after skin pricking disclosed focal keratinocyte detachment typical to EB. Additionally, we identified a deleterious-predicted variant in ENPP1, a gene associated with disturbed transfer of melanosomes to keratinocytes in Cole disease. Our report expands the clinical spectrum of inherited EB simplex with a possible di-genic synergism contributing to co-presentation with guttate leukoderma.

Original languageEnglish
Pages (from-to)1927-1931
Number of pages5
JournalExperimental Dermatology
Issue number12
StatePublished - Dec 2022
Externally publishedYes

Bibliographical note

Funding Information:
The study was supported by a generous donation from the Trottner family. We appreciate language editing assistance provided by DerMEDit (www.DerMEDit.com).

Publisher Copyright:
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


  • classification
  • epidermolysis bullosa
  • genetic skin diseases
  • skin abnormalities


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