title: A de novo FLCN mutation in a patient with spontaneous pneumothorax and renal cancer; a clinical and molecular evaluation.
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.
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands, fh.menko@vumc.nl.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Menko
authors.forename: Paul C
authors.initials: PC
authors.lastname: Johannesma
authors.forename: R Jeroen A
authors.initials: RJ
authors.lastname: van Moorselaar
authors.forename: Rinze
authors.initials: R
authors.lastname: Reinhard
authors.forename: Jan Hein
authors.initials: JH
authors.lastname: van Waesberghe
authors.forename: Erik
authors.initials: E
authors.lastname: Thunnissen
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Houweling
authors.forename: Edward M
authors.initials: EM
authors.lastname: Leter
authors.forename: Quinten
authors.initials: Q
authors.lastname: Waisfisz
authors.forename: Martijn B
authors.initials: MB
authors.lastname: van Doorn
authors.forename: Theo M
authors.initials: TM
authors.lastname: Starink
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Postmus
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Coull
authors.forename: Maurice A M
authors.initials: MA
authors.lastname: van Steensel
authors.forename: Johan J P
authors.initials: JJ
authors.lastname: Gille
mesh_terms: D000328:Adult; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D011030:Pneumothorax / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins