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

TY - JOUR

T1 - A de novo FLCN mutation in a patient with spontaneous pneumothorax and renal cancer; a clinical and molecular evaluation

AU - Menko, Fred H.

AU - Johannesma, Paul C.

AU - van Moorselaar, R. Jeroen A

AU - Reinhard, Rinze

AU - van Waesberghe, Jan Hein

AU - Thunnissen, Erik

AU - Houweling, Arjan C.

AU - Leter, Edward M.

AU - Waisfisz, Quinten

AU - van Doorn, Martijn B.

AU - Starink, Theo M.

AU - Postmus, Pieter E.

AU - Coull, Barry J.

AU - van Steensel, Maurice A. M.

AU - Gille, Johan J. P.

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - Birt-Hogg-Dubé syndrome

KW - De novo mutation

KW - Folliculin

KW - Pneumothorax

KW - Renal cancer

UR - https://www.scopus.com/pages/publications/84885949647

U2 - 10.1007/s10689-012-9593-8

DO - 10.1007/s10689-012-9593-8

M3 - Article

C2 - 23264078

AN - SCOPUS:84885949647

SN - 1389-9600

VL - 12

SP - 373

EP - 379

JO - Familial Cancer

JF - Familial Cancer

IS - 3

ER -