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

Abstract

Birt–Hogg–Dubé syndrome (BHDS) is a rare autosomal dominant inherited disorder caused by a mutation in folliculin (FLCN) gene transmitted via 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 FLCN 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 FLCN genetic mutation, and has also been identified to have a pathogenic variant in BRCA2 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.

Prevalence of a BRCA2 Pathogenic Variant in Hereditary-Breast-and-Ovarian-Cancer-Syndrome Families with Increased Risk of Pancreatic Cancer in a Restricted Italian Area

“…Genetic analysis of the probands and of a part of their relatives was performed through the enrichment protocol TruSight Cancer (Illumina, San Diego, CA, USA), as previously reported [ 23 ]. A further part of the subjects was analyzed using the v1.1 SOPHiA Hereditary Cancer Solution (HCS) enrichment protocol (SOPHiA GENETICS, Saint-Sulpice, Switzerland) and output files (FASTQ) uploaded on the SOPHiA DDM Platform v5.5.0 (SOPHiA GENETICS, Saint-Sulpice, Switzerland) for the analysis, as already described by our group [ 24 ] Sequencing was performed using the MiSeq sequencer platform (Illumina) and MiSeq Reagent Kit v2 or MiSeq Reagent Kit v3 600 cycles. According to the International Agency for Research on Cancer (IARC) recommendations [ 25 ], BRCA1/2 variants were classified as pathogenic (PV; class 5) and likely pathogenic (LPV; class 4) through the major variants databases and tool prediction software [ 26 ].…”