Novel Frizzled-4 Gene Mutations in Chinese Patients With Familial Exudative Vitreoretinopathy
Novel Frizzled-4 Gene Mutations in Chinese Patients With Familial Exudative Vitreoretinopathy
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中国家族性渗出性玻璃体视网膜病变患者中新的Frizzled-4基因突变
DOI：
10.1001/archophthalmol.2010.240
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发表时间：
2010-10-01
影响因子：
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通讯作者：
Liang, Chen
中科院分区：
文献类型：
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作者：
Jia, Li-Yun;Li, Xiao-Xin;Liang, Chen
目的：研究中国家族性渗出性玻璃体视网膜病变(FEVR)患者Frizzled4基因(FZD4)的突变情况，探讨其突变相关的临床特征。用聚合酶链式反应和直接测序法对FZD4编码区进行突变筛查。进行多序列比对，以评估不同FZD4同源物和人类Frizzled家族之间的残基保守性。结果：共检测到12个可能致病突变，其中9个为新发现：1个缺失(P14fsX57)，1个无义突变(S491X)，7个错义突变(G22E、E180K、T237R、R253C、F328S、A339T和D470N)。还检测到三个已报道的FZD4突变：H69Y、M105V和W496X。值得注意的是，两名携带复合杂合性突变(H69Y+E180K或W496X)的患者的眼部表型比单一H69Y突变携带者更严重。结论：在本研究的48例中国患者中，有15例(31.3%)FZD4突变与FEVR有关，与其他种族相似。这项研究支持FZD4在中国人群中具有高度多态的性质，并具有不同的突变特征。
Objectives: To search for mutations in the Frizzled-4 gene (FZD4) in Chinese patients with familial exudative vitreoretinopathy (FEVR) and to delineate the mutation-associated clinical features.Methods: Forty-eight Chinese patients with FEVR and 100 unrelated control subjects were recruited and had complete ophthalmic examinations performed. The coding regions of FZD4 were screened for mutations by polymerase chain reaction and direct sequencing. Multiple sequence alignment was conducted to evaluate the conservation of residues among different FZD4 homologs and the human Frizzled family. Genotype-phenotype correlations were also analyzed.Results: Twelve putative disease-causing mutations were identified in total, 9 of which were novel: 1 deletion (P14fsX57), 1 nonsense mutation (S491X), and 7 missense mutations (G22E, E180K, T237R, R253C, F328S, A339T, and D470N). Three reported FZD4 mutations were also detected: H69Y, M105V, and W496X. Remarkably, 2 patients who harbored compound heterozygous mutations (H69Y with E180K or W496X) had a more severe ocular phenotype than carriers of a single H69Y mutation.Conclusions: FZD4 mutations were responsible for FEVR in 15 of 48 Chinese patients (31.3%) in this study, similar to other ethnic groups. This study supports the highly polymorphic nature of FZD4 with a differential mutation profile in the Chinese population.