卵泡蛋白基因的移码突变导致BHD综合征家系的多发性肺囊肿  

A frameshift mutation in FLCN gene caused isolated multiple pulmonary cysts in a Birt-Hogg-Dubésyndrome pedigree

作　　者：褚娇娇 纳建荣[1] 严梅 尹梅[1] 周玮[1] CHU Jiaojiao;NA Jianrong;YAN Mei;YIN Mei;ZHOU Wei(Department of Respiratory and Critical Care Medicine,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学总医院呼吸与危重症医学科,宁夏银川750004

出　　处：《宁夏医学杂志》2023年第3期226-228,F0003,共4页Ningxia Medical Journal

基　　金：宁夏自然科学基金项目(2022AAC03599)。

摘　　要：目的Birt-Hogg-Dubé综合征(BHD)是一种常染色体显性遗传病,由卵泡蛋白(FLCN)基因突变引起,其特征以多发肺囊肿、皮肤纤维滤泡瘤和肾肿瘤为表现。方法我们对此家系进行了外显子组测序以确定先证者的致病基因变异,并进行了Sanger测序,以验证先证者和其家系成员的致病突变。同时采用Sanger测序验证了408例与该病无关的汉族健康对照组的突变。结果外显子组测序和Sanger测序分析显示在所有发病的家庭成员中,均存在移码突变(c.1579_1580invA,p.Arg527Glnfs68*)。蛋白印迹检测和免疫组化检测结果显示,该突变导致FLCN蛋白水平显著下降。结论FLCN基因(c.1579_1580invA,p.Arg527Glnfs68*)中的一个移码突变存在于一个仅以多个肺囊肿为表现的BHD综合征家系中;证实了该突变在BHD综合征家系中的致病性。Objective Birt-Hogg-Dubésyndrome(BHDS)is an autosomal dominant disease caused by mutations in Folliculin(FLCN)gene,which is characterized by multiple pulmonary cysts,skin fibrofolliculomas,and renal tumors.We here report clinical and genetic studies results of a BHD family ascertained with isolated multiple pulmonary cysts carrying a variant in FLCN.Methods We performed exome sequencing to identify pathogenic variant of the proband,and Sanger sequencing was performed to validate the pathogenic variant in proband as well as the family members.Meanwhile,Sanger sequencing was applied to verify the mutation in 408 unrelated health controls of Han Chinese ancestry.Results Exome sequencing and Sanger sequencing showed a frameshift mutation(c.1579_1580invA,p.Arg527Glnfs68*)in all affected family members.Quantitative real-time PCR showed that mRNA level of FLCN gene in the lung of the patients decreased compared with health controls.Western blot and immunohistochemistry showed the mutation caused significant decrease in the level of FLCN protein.Conclusion Our study identified a frameshift variant in FLCN gene(c.1579_1580invA,p.Arg527Glnfs68*)in a BHDS pedigree with isolated multiple pulmonary cysts.The co-segregation between phenotype and genotype and subsequent functional analyses confirmed the pathogenicity of this mutation in the BHDS pedigree.

关 键 词：BHD综合征 多发性肺囊肿 FLCN基因 移码突变 

分 类 号：R737.11[医药卫生—肿瘤]