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首页> 外文期刊>Molecular Genetics & Genomic Medicine >Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency
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Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency

机译:新型FOXL2突变引起早熟卵巢功能不全的睑缘下垂-上睑下垂-表皮逆转综合征

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摘要

Background Blepharophimosis‐ptosis‐epicanthus inversus syndrome (BPES) is a malformation of the eyelids. Forkhead Box?L2 ( FOXL2 ) is the only gene known to be associated with BPES. Methods We identified two Han Chinese BPES families with premature ovarian insufficiency (POI). Sanger sequencing and in?vitro functional analysis were performed to identify the genetic cause. Results Sanger sequencing identified two novel mutations (c.462_468del, c.988_989insG) in FOXL2, one in each family. The in?vitro functional analysis confirmed that both novel mutations were associated with impaired transactivation of downstream genes. Specifically, the single‐base insertion, c.988_989insG, led to subcellular mislocalization and aggregation of the encoded protein, which validated the hypothesis that the two novel FOXL2 mutations are deleterious and associated with POI in the two BPES families. Conclusion The novel mutations identified in the present study will enhance the present knowledge of the mutation spectrum of FOXL2 . The in?vitro experiments provide further insights into the molecular mechanism by which the two new variants mediate disease pathogenesis and may contribute to elucidating the genotype‐phenotype correlation between the two novel FOXL2 mutations and POI.
机译:背景支气管上皮细胞病-上睑下垂-picpichuths逆综合征(BPES)是眼睑的畸形。 Forkhead Box?L2(FOXL2)是唯一已知与BPES相关的基因。方法我们确定了两个汉族BPES家族,其卵巢早衰(POI)。进行了桑格测序和体外功能分析,以确定遗传原因。结果Sanger测序在FOXL2中鉴定出两个新突变(c.462_468del,c.988_989insG),每个家族中一个。体外功能分析证实,这两个新突变均与下游基因的反式激活有关。具体而言,单碱基插入c.988_989insG导致编码蛋白的亚细胞定位错误和聚集,这验证了两个新的FOXL2突变有害且与两个BPES家族中的POI相关的假设。结论本研究鉴定的新突变将增强对FOXL2突变谱的了解。体外实验进一步阐明了这两种新变体介导疾病发病机理的分子机制,并可能有助于阐明这两种新的FOXL2突变与POI之间的基因型-表型相关性。

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