{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:34:10Z","timestamp":1780403650680,"version":"3.54.1"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:00:00Z","timestamp":1686614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Science and ICT","doi-asserted-by":"publisher","award":["NRF-2018R1C1B5083292"],"award-info":[{"award-number":["NRF-2018R1C1B5083292"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Birt\u2013Hogg\u2013Dube (BHD) is a rare genetic disorder characterized by multiple lung cysts, typical skin manifestations, and renal tumors. We prospectively enrolled thirty-one subjects from four South Korean institutions with typical lung cysts, and next-generation sequencing was conducted. We prospectively enrolled thirty-one subjects from four Korean institutions with typical lung cysts. Next-generation sequencing was performed to investigate mutations in the following genes: FLCN, TSC1, TSC2, CFTR, EFEMP2, ELN, FBLN5, LTBP4, and SERPINA1. BHD was diagnosed in 11 of the 31 enrolled subjects (35.5%; FLCN mutations). Notably, we identified three novel mutations (c.1098G&gt;A, c.139G&gt;T, and c.1335del) that have not been previously reported. In addition to FLCN mutations, we also observed mutations in CFTR (16.1%), LTBP4 (9.7%), TSC2 (9.7%), TSC1 (3.2%), ELN (3.2%), and SERPINA1 (3.2%). According to a systematic review of 45 South Korean patients with BHD, the prevalence of pneumothorax (72.7%) was greater in South Korea than in the rest of the world (50.9%; p = 0.003). The prevalence of skin manifestations (13.6%) and renal tumors (9.1%) was lower in Korea than in the rest of the world, at 47.9% [p &lt; 0.001] and 22.5% [p = 0.027], respectively). This study confirmed a significant prediction model for BHD based on age, number of lung cysts (&gt;40), and maximal diameter of lung cysts (&gt;2 cm) regardless of skin manifestations and renal tumors. Importantly, three novel mutations (c.1098G&gt;A, c.139G&gt;T, and c.1335del) were identified. In conclusion, South Korean patients with BHD display characteristics that are different from those observed in patients of other nationalities. Detailed characterization of lung cysts is needed to define BHD, especially in South Korea, even if patients do not present with skin or renal lesions.<\/jats:p>","DOI":"10.3390\/diagnostics13122047","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T01:32:15Z","timestamp":1686706335000},"page":"2047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Outstanding Characteristics of Birt\u2013Hogg\u2013Dube Syndrome in Korea"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-1003","authenticated-orcid":false,"given":"Hye Jung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6114-2059","authenticated-orcid":false,"given":"Yong Jun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3598-2529","authenticated-orcid":false,"given":"Tae Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8998-9510","authenticated-orcid":false,"given":"Sung Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-2471","authenticated-orcid":false,"given":"Duk Hwan","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-A","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-9955","authenticated-orcid":false,"given":"Sang Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-7615","authenticated-orcid":false,"given":"Moo Suk","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Yee","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3340-4223","authenticated-orcid":false,"given":"Yoon Soo","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok Jeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Ye","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3487-2574","authenticated-orcid":false,"given":"Su Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3673-7595","authenticated-orcid":false,"given":"Taehee","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07442, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Ryeol","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangjoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1525-1745","authenticated-orcid":false,"given":"Min Kwang","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S1470-2045(09)70188-3","article-title":"Birt-hogg-dube syndrome: Diagnosis and management","volume":"10","author":"Menko","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1136\/jmg.2009.070565","article-title":"Clinical and genetic spectrum of birt-hogg-dube syndrome patients in whom pneumothorax and\/or multiple lung cysts are the presenting feature","volume":"47","author":"Kunogi","year":"2010","journal-title":"J. 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