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A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review

Birt–Hogg–Dubé syndrome (BHDS, MIM #135150), caused by germline mutations of FLCN gene, is a rare autosomal dominant inherited disorder characterized by skin fibrofolliculomas, renal cancer, pulmonary cysts and spontaneous pneumothorax. The syndrome is considered to be under-diagnosed due to variabl...

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Autores principales: Cai, Minghui, Zhang, Xinxin, Fan, Lizhen, Cheng, Shuwen, Kiram, Abdukahar, Cen, Shaoqin, Chen, Baofu, Ye, Minhua, Gao, Qian, Zhu, Chengchu, Yi, Long, Ma, Dehua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078137/
https://www.ncbi.nlm.nih.gov/pubmed/33927747
http://dx.doi.org/10.3389/fgene.2021.636900
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author Cai, Minghui
Zhang, Xinxin
Fan, Lizhen
Cheng, Shuwen
Kiram, Abdukahar
Cen, Shaoqin
Chen, Baofu
Ye, Minhua
Gao, Qian
Zhu, Chengchu
Yi, Long
Ma, Dehua
author_facet Cai, Minghui
Zhang, Xinxin
Fan, Lizhen
Cheng, Shuwen
Kiram, Abdukahar
Cen, Shaoqin
Chen, Baofu
Ye, Minhua
Gao, Qian
Zhu, Chengchu
Yi, Long
Ma, Dehua
author_sort Cai, Minghui
collection PubMed
description Birt–Hogg–Dubé syndrome (BHDS, MIM #135150), caused by germline mutations of FLCN gene, is a rare autosomal dominant inherited disorder characterized by skin fibrofolliculomas, renal cancer, pulmonary cysts and spontaneous pneumothorax. The syndrome is considered to be under-diagnosed due to variable and atypical manifestations. Herein we present a BHDS family. Targeted next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) revealed a novel FLCN intragenic deletion spanning exons 10-14 in four members including the proband with pulmonary cysts and spontaneous pneumothorax, one member with suspicious skin lesions and a few pulmonary cysts, as well as two asymptomatic family members. In addition, a linkage analysis further demonstrated one member with pulmonary bullae to be a BHDS-ruled-out case, whose bullae presented more likely as an aspect of paraseptal emphysema. Furthermore, the targeted NGS and MLPA data including our previous and present findings were reviewed and analyzed to compare the advantages and disadvantages of the two methods, and a brief review of the relevant literature is included. Considering the capability of the targeted NGS method to detect large intragenic deletions as well as determining deletion junctions, and the occasional false positives of MLPA, we highly recommend targeted NGS to be used for clinical molecular diagnosis in suspected BHDS patients.
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spelling pubmed-80781372021-04-28 A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review Cai, Minghui Zhang, Xinxin Fan, Lizhen Cheng, Shuwen Kiram, Abdukahar Cen, Shaoqin Chen, Baofu Ye, Minhua Gao, Qian Zhu, Chengchu Yi, Long Ma, Dehua Front Genet Genetics Birt–Hogg–Dubé syndrome (BHDS, MIM #135150), caused by germline mutations of FLCN gene, is a rare autosomal dominant inherited disorder characterized by skin fibrofolliculomas, renal cancer, pulmonary cysts and spontaneous pneumothorax. The syndrome is considered to be under-diagnosed due to variable and atypical manifestations. Herein we present a BHDS family. Targeted next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) revealed a novel FLCN intragenic deletion spanning exons 10-14 in four members including the proband with pulmonary cysts and spontaneous pneumothorax, one member with suspicious skin lesions and a few pulmonary cysts, as well as two asymptomatic family members. In addition, a linkage analysis further demonstrated one member with pulmonary bullae to be a BHDS-ruled-out case, whose bullae presented more likely as an aspect of paraseptal emphysema. Furthermore, the targeted NGS and MLPA data including our previous and present findings were reviewed and analyzed to compare the advantages and disadvantages of the two methods, and a brief review of the relevant literature is included. Considering the capability of the targeted NGS method to detect large intragenic deletions as well as determining deletion junctions, and the occasional false positives of MLPA, we highly recommend targeted NGS to be used for clinical molecular diagnosis in suspected BHDS patients. Frontiers Media S.A. 2021-04-01 /pmc/articles/PMC8078137/ /pubmed/33927747 http://dx.doi.org/10.3389/fgene.2021.636900 Text en Copyright © 2021 Cai, Zhang, Fan, Cheng, Kiram, Cen, Chen, Ye, Gao, Zhu, Yi and Ma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Cai, Minghui
Zhang, Xinxin
Fan, Lizhen
Cheng, Shuwen
Kiram, Abdukahar
Cen, Shaoqin
Chen, Baofu
Ye, Minhua
Gao, Qian
Zhu, Chengchu
Yi, Long
Ma, Dehua
A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review
title A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review
title_full A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review
title_fullStr A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review
title_full_unstemmed A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review
title_short A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review
title_sort novel flcn intragenic deletion identified by ngs in a bhds family and literature review
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078137/
https://www.ncbi.nlm.nih.gov/pubmed/33927747
http://dx.doi.org/10.3389/fgene.2021.636900
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