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Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome

BACKGROUND: Birt–Hogg–Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We pre...

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Autores principales: Radzikowska, Elżbieta, Lechowicz, Urszula, Winek, Jolanta, Opoka, Lucyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258955/
https://www.ncbi.nlm.nih.gov/pubmed/34229741
http://dx.doi.org/10.1186/s13023-021-01931-0
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author Radzikowska, Elżbieta
Lechowicz, Urszula
Winek, Jolanta
Opoka, Lucyna
author_facet Radzikowska, Elżbieta
Lechowicz, Urszula
Winek, Jolanta
Opoka, Lucyna
author_sort Radzikowska, Elżbieta
collection PubMed
description BACKGROUND: Birt–Hogg–Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS. MATERIALS AND METHODS: The first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations. RESULTS: BHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41). CONCLUSIONS: All analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-021-01931-0.
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spelling pubmed-82589552021-07-06 Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome Radzikowska, Elżbieta Lechowicz, Urszula Winek, Jolanta Opoka, Lucyna Orphanet J Rare Dis Research BACKGROUND: Birt–Hogg–Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS. MATERIALS AND METHODS: The first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations. RESULTS: BHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41). CONCLUSIONS: All analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-021-01931-0. BioMed Central 2021-07-06 /pmc/articles/PMC8258955/ /pubmed/34229741 http://dx.doi.org/10.1186/s13023-021-01931-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Radzikowska, Elżbieta
Lechowicz, Urszula
Winek, Jolanta
Opoka, Lucyna
Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome
title Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome
title_full Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome
title_fullStr Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome
title_full_unstemmed Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome
title_short Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome
title_sort novel folliculin gene mutations in polish patients with birt–hogg–dubé syndrome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258955/
https://www.ncbi.nlm.nih.gov/pubmed/34229741
http://dx.doi.org/10.1186/s13023-021-01931-0
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