Birt-Hogg-Dube syndrome: Molecular analysis and diagnosis of related lesions

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590408
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Chiba University
• Principal Investigator: NAKATANI Yukio 千葉大学, 医学(系)研究科(研究院), 教授 (20137037)
• Co-Investigator(Kenkyū-buntansha): FURUYA Mitsuko 横浜市立大学, 医学研究科, 准教授 (10361445) ; NAGASHIMA Yoji 東京女子医科大学, 附属病院, 教授 (10217995) ; OHTA Satoshi 千葉大学, 医学部附属病院, 准教授 (90324342)
• Co-Investigator(Renkei-kenkyūsha): YAMAGUCHI Atsushi 千葉大学, 大学院医学研究院, 准教授 (00314336) ; HIROSHIMA Kenzo 東京女子医科大学, 八千代医療センター, 教授 (80218833)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: フォリキュリン / バート・ホッグ・デュベ症候群 / 腎腫瘍 / 肺嚢胞

Outline of Final Research Achievements

Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant inherited disorder associated with a germline mutation of the folliculin gene (FLCN), characterized by fibrofolliculomas, renal tumors, pulmonary cysts and pneumothorax. The number of BHDS individuals is not studied in Japan. We have diagnosed 100 BHDS families by genetic testing. Pulmonary cysts in BHDS are bilateral and multifocal. Individuals with BHDS have a high risk of developing spontaneous, recurrent pneumothorax. Although BHD pulmonary cysts are frequently misdiagnosed as nonspecific cystic diseases, they are distinctly different in histopathology from other bullous changes. Renal tumors in BHDS showed overexpression of glycoprotein non-metastatic B (GPNMB) and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. The distinctive expression patterns of GPNMB and FLCN might identify patients with renal tumors who need further work-up for BHDS.

Free Research Field

診断病理学