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A de novo FLCN mutation in a patient with spontaneous pneumothorax and renal cancer; a clinical and molecular evaluation

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Abstract

Birt–Hogg–Dubé syndrome (BHD) is an autosomal dominant condition due to germline FLCN (folliculin) mutations, characterized by skin fibrofolliculomas, lung cysts, pneumothorax and renal cancer. We identified a de novo FLCN mutation, c.499C>T (p.Gln167X), in a patient who presented with spontaneous pneumothorax. Subsequently, typical skin features and asymptomatic renal cancer were diagnosed. Probably, de novo FLCN mutations are rare. However, they may be under-diagnosed if BHD is not considered in sporadic patients who present with one or more of the syndromic features. Genetic and immunohistochemical analysis of the renal tumour indicated features compatible with a tumour suppressor role of FLCN. The finding that mutant FLCN was expressed in the tumour might indicate residual functionality of mutant FLCN, a notion which will be explored in future studies.

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Acknowledgments

MvS and BJC are supported by grants from the Dutch Cancer Society KWF (UM2009-4352), the Association for International Cancer Research AICR (11-0687) and the Annadal Foundation.

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Authors and Affiliations

  1. Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands

    Fred H. Menko, Arjan C. Houweling, Edward M. Leter, Quinten Waisfisz & Johan J. P. Gille

  2. Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands

    Paul C. Johannesma & Pieter E. Postmus

  3. Department of Urology, VU University Medical Center, Amsterdam, The Netherlands

    R. Jeroen A. van Moorselaar

  4. Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands

    Rinze Reinhard & Jan Hein van Waesberghe

  5. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

    Erik Thunnissen

  6. Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands

    Martijn B. van Doorn & Theo M. Starink

  7. Department of Dermatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

    Barry J. Coull & Maurice A. M. van Steensel

  8. Department of Clinical Genetics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

    Maurice A. M. van Steensel

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  1. Fred H. Menko
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  2. Paul C. Johannesma
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  7. Arjan C. Houweling
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  14. Maurice A. M. van Steensel
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  15. Johan J. P. Gille
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Correspondence to Fred H. Menko.

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Menko, F.H., Johannesma, P.C., van Moorselaar, R.J.A. et al. A de novo FLCN mutation in a patient with spontaneous pneumothorax and renal cancer; a clinical and molecular evaluation. Familial Cancer 12, 373–379 (2013). https://doi.org/10.1007/s10689-012-9593-8

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  • DOI: https://doi.org/10.1007/s10689-012-9593-8

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