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Familial Cancer

, Volume 12, Issue 3, pp 373–379 | Cite as

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

  • Fred H. Menko
  • Paul C. Johannesma
  • R. Jeroen A. van Moorselaar
  • Rinze Reinhard
  • Jan Hein van Waesberghe
  • Erik Thunnissen
  • Arjan C. Houweling
  • Edward M. Leter
  • Quinten Waisfisz
  • Martijn B. van Doorn
  • Theo M. Starink
  • Pieter E. Postmus
  • Barry J. Coull
  • Maurice A. M. van Steensel
  • Johan J. P. Gille
Original Article

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.

Keywords

Birt–Hogg–Dubé syndrome Folliculin de novo mutation Pneumothorax Renal cancer 

Notes

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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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Fred H. Menko
    • 1
  • Paul C. Johannesma
    • 2
  • R. Jeroen A. van Moorselaar
    • 3
  • Rinze Reinhard
    • 4
  • Jan Hein van Waesberghe
    • 4
  • Erik Thunnissen
    • 5
  • Arjan C. Houweling
    • 1
  • Edward M. Leter
    • 1
  • Quinten Waisfisz
    • 1
  • Martijn B. van Doorn
    • 6
  • Theo M. Starink
    • 6
  • Pieter E. Postmus
    • 2
  • Barry J. Coull
    • 7
  • Maurice A. M. van Steensel
    • 7
    • 8
  • Johan J. P. Gille
    • 1
  1. 1.Department of Clinical GeneticsVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of PulmonologyVU University Medical CenterAmsterdamThe Netherlands
  3. 3.Department of UrologyVU University Medical CenterAmsterdamThe Netherlands
  4. 4.Department of RadiologyVU University Medical CenterAmsterdamThe Netherlands
  5. 5.Department of PathologyVU University Medical CenterAmsterdamThe Netherlands
  6. 6.Department of DermatologyVU University Medical CenterAmsterdamThe Netherlands
  7. 7.Department of Dermatology, GROW School for Oncology and Developmental BiologyMaastricht University Medical CentreMaastrichtThe Netherlands
  8. 8.Department of Clinical Genetics, GROW School for Oncology and Developmental BiologyMaastricht University Medical CentreMaastrichtThe Netherlands

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