Birt–Hogg–Dubé syndrome: novel FLCN frameshift deletion in daughter and father with renal cell carcinomas

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• 作者：Ernst Näf ; Dominik Laubscher ; Helmut Hopfer ; Markus Streit ; Gabor Matyas
• 关键词：Birt–Hogg–Dubé syndrome ; BHD ; Folliculin ; FLCN ; Haploinsufficiency ; Inherited kidney cancer
• 刊名：Familial Cancer
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：15
• 期：1
• 页码：127-132
• 全文大小：967 KB
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• 作者单位：Ernst Näf (1)
  Dominik Laubscher (2)
  Helmut Hopfer (3)
  Markus Streit (4)
  Gabor Matyas (2) (5)
  
  1. Department of Practice Development in Nursing, Solothurner Spitäler AG, Olten, Switzerland
  2. Genetic Center of the Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland
  3. Institute for Pathology, University Hospital, Basel, Switzerland
  4. Department of Dermatology, Kantonsspital, Aarau, Switzerland
  5. Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Human Genetics
  Epidemiology
  
• 出版者：Springer Netherlands
• ISSN：1573-7292

文摘

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. Keywords Birt–Hogg–Dubé syndrome BHD Folliculin FLCN Haploinsufficiency Inherited kidney cancer