AUTHOR=Bandini Erika , Cangini Ilaria , Arcangeli Valentina , Ravegnani Mila , Andreotti Virginia , Prisinzano Giovanna , Pastorino Lorenza , Martinelli Giovanni , Falcini Fabio , Calistri Daniele , Zampiga Valentina , Danesi Rita 

TITLE=Case Report: A BRCA2 Mutation Identified Through Next-Generation Sequencing in a Birt–Hogg–Dubè Syndrome Family

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.835346

DOI=10.3389/fonc.2022.835346

ISSN=2234-943X

ABSTRACT=<p>Birt–Hogg–Dubé syndrome (BHDS) is a rare autosomal dominant inherited disorder caused by a mutation in folliculin (<italic>FLCN</italic>) gene transmitted <italic>via</italic> germline autosomal dominant pattern. Patients with this syndrome have an increased susceptibility to renal cell carcinoma, lung cysts, spontaneous pneumothorax, and benign skin hamartomas, and its diagnosis is not easy and consequently underestimated. Several mutations have been identified in <italic>FLCN</italic> gene, among which the majority of alterations are frameshift (insertion/deletion), nonsense, or splice-site mutations that generally produce unfunctional truncated FLCN proteins. Our aim is to present a case of a BHDS family whose proband is a 56-year-old patient who has been experiencing multiple disorders, has an <italic>FLCN</italic> genetic mutation, and has also been identified to have a pathogenic variant in <italic>BRCA2</italic> gene. Our further purpose is to emphasize the importance of the next-generation sequencing (NGS) approach to identify potential multiple germline mutations in complex and rare oncologic disorders, allowing strict and more targeted cancer screening programs.</p>