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Phenotype variability in tumor disorders of the skin appendages associated with mutations in the CYLD gene

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Abstract

Mutations in the tumor suppressor gene CYLD underlie phenotypically heterogeneous hereditary tumor disorders of the skin appendages. These diseases are inherited autosomal dominantly and include Brooke–Spiegler syndrome (BSS; OMIM 605041), familial cylindromatosis (FC; OMIM 132700) and multiple familial trichoepithelioma (MFT; OMIM 601606). Clinically, cylindromas, trichoepitheliomas and spiradenomas can be found in affected individuals. We sought to elucidate the molecular genetic basis in individuals with newly diagnosed cylindromas, trichoepitheliomas and/or spiradenomas. Mutation analysis using polymerase chain reaction (PCR)-based techniques was performed in seven German patients and one Turkish patient. We detected two missense, two nonsense, two deletions and two duplication mutations in the CYLD gene, of which seven have not yet been reported. No genotype–phenotype correlation was detected amongst the patients. Our data provide additional information on the clinical and molecular genetic heterogeneity of disorders associated with CYLD mutations.

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Fig. 1
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Abbreviations

aa:

Amino acids

BSS:

Brooke–Spiegler syndrome

CAP-GLY:

Cytoskeleton-associated protein glycine-rich

FC:

Familial cylindromatosis

MFT:

Multiple familial trichoepithelioma

PCR:

Polymerase chain reaction

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Acknowledgements

We are grateful to the patients for their interest and participation in this study.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Dermatology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands

    Lizelotte J. M. T. Parren

  2. Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands

    Lizelotte J. M. T. Parren & Michel van Geel

  3. GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands

    Lizelotte J. M. T. Parren & Michel van Geel

  4. Department of Dermatology, Ludwig-Maximilian University Munich, Munich, Germany

    Kathrin Giehl

  5. Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands

    Michel van Geel

  6. Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Jorge Frank

Authors
  1. Lizelotte J. M. T. Parren
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  2. Kathrin Giehl
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  3. Michel van Geel
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  4. Jorge Frank
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Correspondence to Jorge Frank.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Parren, L.J.M.T., Giehl, K., van Geel, M. et al. Phenotype variability in tumor disorders of the skin appendages associated with mutations in the CYLD gene. Arch Dermatol Res 310, 599–606 (2018). https://doi.org/10.1007/s00403-018-1848-2

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  • DOI: https://doi.org/10.1007/s00403-018-1848-2

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