| Title: | Inherited predisposition to pneumothorax: estimating the frequency of Birt-Hogg-Dubé syndrome from genomics and population cohorts |
| Journal: | Thorax |
| Published: | 10 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40210444/ |
| DOI: | https://doi.org/10.1136/thorax-2024-221738 |
Publication 14714
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Abstract
Birt-Hogg-Dubé syndrome (BHDS) is the most common monogenic cause of pneumothorax. Most affected families have pathogenic variants in the FLCN gene. Using large genomic registries (UK Biobank (UKB), 100,000 Genomes Project and East London Genes & Health) including >550 000 individuals, we demonstrate that the frequency of clinically validated loss-of-function FLCN variants is 1 in 2710 to 4190. While the lifetime risk of pneumothorax in FLCN mutation carriers in the UKB and a BHDS clinical cohort was substantial (28.4% and 37.3%, respectively, to age 65 years), the lifetime risk of renal cancer was significantly lower in UKB than in BHDS patients (1% vs 32.1%). These findings highlight the importance of clinical context in managing individuals with FLCN mutations.</p>
9 Authors
- Bryndis Yngvadottir
- Lucy Richman
- Avgi Andreou
- Jessica Woodley
- Anita Luharia
- Derek Lim
- Genes & Health Research Team
- Eamonn R Maher
- Stefan J Marciniak
1 Application
| Application ID | Title |
|---|---|
| 95547 | Identification of phenotypic associations of rare variants in genes predisposing to rare inherited disorders in UK Biobank exome and genome data. |
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