Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome
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/dup...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02710-9 |
| _version_ | 1797827360825802752 |
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| author | Yue Wang Mengru Cai Xianliang Jiang Guangyu Lv Daiju Hu Guofeng Zhang Jinli Liu Wei Wei Jun Xiao Bing Shen Jay H. Ryu Xiaowen Hu |
| author_facet | Yue Wang Mengru Cai Xianliang Jiang Guangyu Lv Daiju Hu Guofeng Zhang Jinli Liu Wei Wei Jun Xiao Bing Shen Jay H. Ryu Xiaowen Hu |
| author_sort | Yue Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T12:47:03Z |
| format | Article |
| id | doaj.art-30dbbecd2c164a96b5e3f96958b5407d |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-09T12:47:03Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-30dbbecd2c164a96b5e3f96958b5407d2023-05-14T11:27:34ZengBMCOrphanet Journal of Rare Diseases1750-11722023-05-011811910.1186/s13023-023-02710-9Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndromeYue Wang0Mengru Cai1Xianliang Jiang2Guangyu Lv3Daiju Hu4Guofeng Zhang5Jinli Liu6Wei Wei7Jun Xiao8Bing Shen9Jay H. Ryu10Xiaowen Hu11Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Dermatology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Radiology, The First Affiliated Hospital of USTC, University of Science and Technology of ChinaDepartment of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaSchool of Basic Medicine, Anhui Medical UniversityDivision of Pulmonary and Critical Care Medicine, Mayo ClinicDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAbstract 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.https://doi.org/10.1186/s13023-023-02710-9Birt-Hogg-Dubé syndromeExons 1–3 deletionGenotype–phenotype correlationPneumothorax |
| spellingShingle | Yue Wang Mengru Cai Xianliang Jiang Guangyu Lv Daiju Hu Guofeng Zhang Jinli Liu Wei Wei Jun Xiao Bing Shen Jay H. Ryu Xiaowen Hu Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome Orphanet Journal of Rare Diseases Birt-Hogg-Dubé syndrome Exons 1–3 deletion Genotype–phenotype correlation Pneumothorax |
| title | Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome |
| title_full | Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome |
| title_fullStr | Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome |
| title_full_unstemmed | Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome |
| title_short | Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome |
| title_sort | exons 1 3 deletion in flcn is associated with increased risk of pneumothorax in chinese patients with birt hogg dube syndrome |
| topic | Birt-Hogg-Dubé syndrome Exons 1–3 deletion Genotype–phenotype correlation Pneumothorax |
| url | https://doi.org/10.1186/s13023-023-02710-9 |
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