1. Exons 1-3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome.
- Author
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Wang Y, Cai M, Jiang X, Lv G, Hu D, Zhang G, Liu J, Wei W, Xiao J, Shen B, Ryu JH, and Hu X
- Subjects
- Humans, East Asian People, Retrospective Studies, Exons genetics, Proto-Oncogene Proteins genetics, Tumor Suppressor Proteins genetics, Pneumothorax genetics, Birt-Hogg-Dube Syndrome genetics, Kidney Neoplasms
- Abstract
Background: The pathogenic variants responsible for Birt-Hogg-Dubé syndrome (BHDS) in folliculin (FLCN) gene mostly consist of point mutations. Although large intragenic deletions/duplications have been reported in several case reports, the relationship between large intragenic deletions/duplications and phenotype in BHDS remains unclear., Methods: We retrospectively identified and reviewed patients with a large intragenic deletion spanning exons 1-3 and analyzed their phenotypic features to compare with those of point mutation carriers in our hospital from January 1, 2017 to August 31, 2022., Results: Twenty unique point mutations (including 4 novel mutations) were detected in 62 patients from 45 families (90%). Exons 1-3 deletion were identified in 8 patients from 5 families (10%) that resided in the same region, Feidong County of Anhui Province, China. Breakpoint analysis indicated that all the deletion breakpoints were flanked by Alu repeats. The prevalence of exons 1-3 deletion carriers in Feidong County was 8.1-times higher than that for BHDS in Anhui Province, suggesting a clustered phenomenon of exons 1-3 deletion. Significantly increased risk of pneumothorax was observed in those with exons 1-3 deletion compared with point mutations (91% vs. 58%, p value 0.047). The risk of renal cancer may be higher in those with exons 1-3 deletion than for those with point mutations (18% vs. 4%, p > 0.05)., Conclusions: Large intragenic deletion of exons 1-3 in FLCN was identified as a local aggregation phenomenon in Feidong County, China, and was associated with a significantly higher risk of pneumothorax compared to those with point mutations., (© 2023. The Author(s).)
- Published
- 2023
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