TY - JOUR
T1 - Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome
AU - Wang, Yue
AU - Cai, Mengru
AU - Jiang, Xianliang
AU - Lv, Guangyu
AU - Hu, Daiju
AU - Zhang, Guofeng
AU - Liu, Jinli
AU - Wei, Wei
AU - Xiao, Jun
AU - Shen, Bing
AU - Ryu, Jay H.
AU - Hu, Xiaowen
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Birt-Hogg-Dubé syndrome
KW - Exons 1–3 deletion
KW - Genotype–phenotype correlation
KW - Pneumothorax
UR - http://www.scopus.com/inward/record.url?scp=85159229358&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85159229358&partnerID=8YFLogxK
U2 - 10.1186/s13023-023-02710-9
DO - 10.1186/s13023-023-02710-9
M3 - Article
C2 - 37170274
AN - SCOPUS:85159229358
SN - 1750-1172
VL - 18
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
IS - 1
M1 - 115
ER -