%0 Journal Article
%T Exons 1-3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome.
%A Wang Y
%A Cai M
%A Jiang X
%A Lv G
%A Hu D
%A Zhang G
%A Liu J
%A Wei W
%A Xiao J
%A Shen B
%A Ryu JH
%A Hu X
%J Orphanet J Rare Dis
%V 18
%N 1
%D 2023 05 12
%M 37170274
%F 4.303
%R 10.1186/s13023-023-02710-9
%X 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.<BR>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.<BR>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).<BR>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.