PDF(Pubmed)
Abstract：
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.
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.
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).
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.
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.
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).
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.
摘要：
背景：毛囊蛋白（FLCN）基因中导致Birt-Hogg-Dubé综合征（BHDS）的致病变异主要由点突变组成。尽管在一些病例报告中报告了大量基因内缺失/重复，BHDS基因内大量缺失/重复与表型之间的关系尚不清楚.
方法：我们回顾性地鉴定并回顾了2017年1月1日至2022年8月31日在我院治疗的跨外显子1-3的大基因内缺失患者，并分析其表型特征，以与点突变携带者进行比较。
结果：在来自45个家庭（90％）的62例患者中检测到20个独特的点突变（包括4个新突变）。在居住在同一区域的5个家庭（10％）的8名患者中发现了外显子1-3缺失，安徽省肥东县,中国。断点分析表明,所有缺失断点侧翼为Alu重复。肥东县外显子1-3缺失携带者的患病率是安徽省BHDS的8.1倍，提示外显子1-3缺失的聚集现象。与点突变相比，外显子1-3缺失的患者发生气胸的风险显着增加（91％vs.58%,p值0.047)。外显子1-3缺失的人患肾癌的风险可能高于点突变的人(18%vs.4%,p>0.05)。
结论：FLCN中外显子1-3的大基因内缺失被确定为肥东县的局部聚集现象，中国,与点突变的患者相比,与气胸的发生风险显著增高相关.
方法：我们回顾性地鉴定并回顾了2017年1月1日至2022年8月31日在我院治疗的跨外显子1-3的大基因内缺失患者，并分析其表型特征，以与点突变携带者进行比较。
结果：在来自45个家庭（90％）的62例患者中检测到20个独特的点突变（包括4个新突变）。在居住在同一区域的5个家庭（10％）的8名患者中发现了外显子1-3缺失，安徽省肥东县,中国。断点分析表明,所有缺失断点侧翼为Alu重复。肥东县外显子1-3缺失携带者的患病率是安徽省BHDS的8.1倍，提示外显子1-3缺失的聚集现象。与点突变相比，外显子1-3缺失的患者发生气胸的风险显着增加（91％vs.58%,p值0.047)。外显子1-3缺失的人患肾癌的风险可能高于点突变的人(18%vs.4%,p>0.05)。
结论：FLCN中外显子1-3的大基因内缺失被确定为肥东县的局部聚集现象，中国,与点突变的患者相比,与气胸的发生风险显著增高相关.
