Detection of Folliculin Gene Mutations in Two Chinese Families with Birt-Hogg-Dube Syndrome.
Detection of Folliculin Gene Mutations in Two Chinese Families with Birt-Hogg-Dube Syndrome.
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中国两个 Birt-Hogg-Dube 综合征家系卵泡素基因突变检测
DOI：
10.1155/2017/8751384
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发表时间：
2017
影响因子：
--
通讯作者：
Luo H
中科院分区：
文献类型：
--
作者：
Liu L;Yang K;Wang X;Shi Z;Yang Y;Yuan Y;Guo T;Xiao X;Luo H
Birt-Hogg-Dube综合征（Birt-Hogg-Dube syndrome，BHD，OMIM#135150）是一种临床少见的疾病，以皮肤纤维毛囊瘤、肺囊肿和复发性气胸、肾囊肿和肾肿瘤为特征。先前的研究表明，卵泡素（FLCN，NM_144997）的变异体是导致这种疾病的主要原因。在本研究中，我们招募了两个BHD家庭，并应用FLCN直接测序来探讨他们的遗传病变。发现了两种FLCN突变：一种是新的缺失突变（c.668delA/p.N223TfsX19），另一种是先前报道的插入突变（c.1579_1580insA/p.R527QfsX75）。共分离试验证实了这两个突变体的致病性。生物信息学分析表明，c.668delA可能会导致FLCN的功能单倍不足，因为携带该突变的mRNA表现出更快的降解速率相比，野生型。Real-time qPCR也证实了先证者FLCN表达的mRNA水平与对照组相比显著降低，这可能破坏了mTOR通路并导致BHD。预测插入突变（c.1579_1580insA）导致FLCN的氨基酸序列延长。目前两个突变的鉴定不仅进一步支持了肿瘤抑制因子FLCN在BHD和原发性自发性气胸中的重要作用，而且扩大了FLCN突变的谱，并将为BHD家族的遗传诊断和咨询提供见解。
Birt-Hogg-Dube syndrome (BHD, OMIM#135150) is a rare disease in clinic; it is characterized by skin fibrofolliculomas, pulmonary cysts with an increased risk of recurrent pneumothorax, renal cysts, and renal neoplasms. Previous studies have demonstrated that variants in folliculin (FLCN, NM_144997) are mainly responsible for this disease. In this research, we enrolled two BHD families and applied direct sequencing of FLCN to explore the genetic lesions in them. Two FLCN mutations were identified: one is a novel deletion variant (c.668delA/p.N223TfsX19), while the other is a previously reported insertion mutation (c.1579_1580insA/p.R527QfsX75). And the pathogenicity of both variants was confirmed by cosegregation assay. Bioinformatics analysis showed that c.668delA may lead to functional haploinsufficiency of FLCN because mRNA carrying this mutation exhibits a faster degradation rate comparing to the wild type. Real-time qPCR also confirmed that the mRNA level of FLCN expression in the proband was decreased significantly compared with the controls, which may disrupt the mTOR pathway and lead to BHD. The insertion mutation (c.1579_1580insA) was predicted to cause a prolonged amino acid sequence of FLCN. The present identification of two mutations not only further supports the important role of tumor suppressor FLCN in BHD and primary spontaneous pneumothorax, but also expands the spectrum of FLCN mutations and will provide insight into genetic diagnosis and counseling of families with BHD.
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影响因子：
4
作者：
Toro, J. R.;Wei, M-H;Glenn, G. M.;Weinreich, M.;Toure, O.;Vocke, C.;Turner, M.;Choyke, P.;Merino, M. J.;Pinto, P. A.;Steinberg, S. M.;Schmidt, L. S.;Linehan, W. M.
通讯作者：
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影响因子：
8.8
作者：
Houweling, A. C.;Gijezen, L. M.;Jonker, M. A.;van Doorn, M. B. A.;Oldenburg, R. A.;van Spaendonck-Zwarts, K. Y.;Leter, E. M.;van Os, T. A.;van Grieken, N. C. T.;Jaspars, E. H.;de Jong, M. M.;Bongers, E. M. H. F.;Johannesma, P. C.;Postmus, P. E.;van Moorselaar, R. J. A.;van Waesberghe, J-H T. M.;Starink, T. M.;van Steensel, M. A. M.;Gille, J. J. P.;Menko, F. H.
通讯作者：
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