Birt-Hogg-Dubé syndrome: novel FLCN frameshift deletion in daughter and father with renal cell carcinomas.
Germline mutation of the FLCN gene causes Birt-Hogg-Dubé syndrome (BHD), a rare autosomal dominant condition characterized by skin fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal tumours. We identified a hitherto unreported pathogenic FLCN frameshift deletion c.563delT (p.Phe188Serfs*35) in a family of a 46-year-old woman presented with macrohematuria due to bilateral chromophobe renal carcinomas. A heritable renal cancer was suspected due to the bilaterality of the tumour and as the father of this woman had suffered from renal cancer. Initially, however, BHD was overlooked by the medical team despite the highly suggestive clinical presentation. We assume that BHD is underdiagnosed, at least partially, due to low awareness of this variable condition and to insufficient use of appropriate genetic testing. Our study indicates that BHD and FLCN testing should be routinely considered in patients with positive family or personal history of renal tumours. In addition, we demonstrate how patients and their families can play a driving role in initiating genetic diagnosis, presymptomatic testing of at-risk relatives, targeted disease management, and genetic counselling of rare diseases such as BHD.
Department of Practice Development in Nursing, Solothurner Spitäler AG, Olten, Switzerland.
Ernst
E
Näf
Genetic Center of the Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland.
Dominik
D
Laubscher
Institute for Pathology, University Hospital, Basel, Switzerland.
Helmut
H
Hopfer
Department of Dermatology, Kantonsspital, Aarau, Switzerland.
Markus
M
Streit
Genetic Center of the Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland. matyas@genetikzentrum.ch.|Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. matyas@genetikzentrum.ch.
Gabor
G
Matyas
D058249:Birt-Hogg-Dube Syndrome / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins
BHD; Birt–Hogg–Dubé syndrome; FLCN; Folliculin; Haploinsufficiency; Inherited kidney cancer