摘要
背景:睑裂综合征(BPES)以眼睑畸形为特征,偶见卵巢早衰。FOXL2的突变是BPES病例的一小部分原因。目的:探讨中国26个家系(78例)BPES的遗传基础。方法:对每个家庭成员进行眼科检查。我们用Sanger测序筛选FOXL2外显子及其侧翼序列。我们还对所有已识别的变异进行了生物信息学研究、结构建模和致病性评估。对文献进行回顾性分析,并进行基因型-表型相关分析。结果:患者有典型的BPES表现。在26个家系中,有10个家系发现了10个突变。其中7个是新突变。这些突变包括6个截短突变,p.Glu69*,p.Gly256Glyfs*14,p.Ala14Serfs*135,p.Pro333Professional*200,p.Pro290Leufs*70和p.Pro157Professional*91,以及一个误解突变pT.yr59Cys。突变分布于基因内,未发现突变热点。基因型-表型相关分析显示移码突变或无意义突变与I型BPES相关,而帧内突变或错义突变与Ⅱ型BPES相关。结论:我们报告了中国迄今最大的BPES序列以及FOXL2的7个新突变。新突变的鉴定不仅扩大了该基因的突变谱(这对于基于突变检测的筛选是有价值的),而且表明中国人群中的大多数突变可能还没有被描述。
关键词: Blepharophimosis综合征,BPES,FOXL2,眼科,突变,结构模型。
Current Molecular Medicine
Title:Seven Novel and Three Known Mutations in FOXL2 in 10 Chinese Families with Blepharophimosis Syndrome
Volume: 18 Issue: 3
关键词: Blepharophimosis综合征,BPES,FOXL2,眼科,突变,结构模型。
摘要: Background: Blepharophimosis syndrome (BPES) is characterized by eyelid malformation with occasional premature ovarian failure. Mutations in FOXL2 underlie a fraction of BPES cases.
Objective: We aimed to investigate the genetic basis of BPES in 26 Chinese families that included 78 patients.
Methods: We performed ophthalmological examinations on each family member. We used Sanger sequencing to screen FOXL2 exons and their flanking sequences. We also performed bioinformatics studies, structural modeling and pathogenicity evaluations on all identified variations. Literature was reviewed and genotype-phenotype correlation analysis was performed.
Results: The patients had typical manifestations of BPES. Ten mutations were identified in ten of the twenty-six families. Among these, seven were novel mutations. These included the six truncating mutations, p.Glu69*, p.Gly256Glyfs*14, p.Ala14Serfs*135, p.Pro333Profs*200, p.Pro290Leufs*70, and p.Pro157Profs*91, and one missense mutation, p.Tyr59Cys. The mutations were scattered within the gene, and no mutational hotspots were found. Genotype-phenotype correlation analysis showed that frameshift or nonsense mutations were correlated with type I BPES, while in-frame or missense mutations were associated with type II BPES.
Conclusion: We report the largest BPES cohort in China thus far as well as seven novel mutations in FOXL2. The identification of novel mutations has not only expanded the mutational spectrum of the gene (which is valuable for mutation detection-based screening) but also suggests that most mutations within the Chinese population may not have been characterized yet.
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Cite this article as:
Seven Novel and Three Known Mutations in FOXL2 in 10 Chinese Families with Blepharophimosis Syndrome, Current Molecular Medicine 2018; 18 (3) . https://dx.doi.org/10.2174/1566524018666180907162619
DOI https://dx.doi.org/10.2174/1566524018666180907162619 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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