Activation of a cryptic splice site of PTEN and loss of heterozygosity in benign skin lesions in Cowden disease

Joerg Trojan, Guido Plotz, Angela Brieger, Jochen Raedle, Stephen J. Meltzer, Manfred Wolter, Stefan Zeuzem

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Cowden disease is an autosomal dominant syndrome characterized by facial trichilemmomas, acral keratoses, papillomatous papules, mucosal lesions, and an increased risk for breast and nonmedullary thyroid cancer. Here, we describe a novel PTEN splicing site mutation in a family with classical Cowden disease and we studied benign skin lesions typical for Cowden disease for loss of heterozygosity. We found a PTEN IVS2 + 1G > A 5′-splicing acceptor mutation resulting in activation of a cryptic splice site. Activation of this cryptic splice site is predicted to result in a frameshift with a premature stop codon, thus disrupting the phosphatase core motif of PTEN. Loss of heterozygosity analysis of two trichilemmomas, one fibroma, and three acanthomas of the index patient demonstrated loss of heterozygosity at the PTEN locus in four of these lesions. In conclusion, our data demonstrate that a PTEN splicing site mutation causes activation of a cryptic splice site, which results in aberrant transcripts.

Original languageEnglish (US)
Pages (from-to)1650-1653
Number of pages4
JournalJournal of Investigative Dermatology
Issue number6
StatePublished - Dec 2001
Externally publishedYes


  • Genes, suppressor, tumor
  • Germline mutation
  • Hamartoma syndrome, multiple
  • Keratosis
  • Loss of heterozygosity
  • RNA splicing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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