Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity
Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity
复制标题
DOI：
10.1136/bjo.87.10.1291
复制
发表时间：
2003-10-01
影响因子：
4.1
通讯作者：
Hayashi, K
中科院分区：
文献类型：
--
作者：
Kondo, H;Hayashi, H;Hayashi, K
目的：研究家族性渗出性玻璃体视网膜病变(FEVR)患者FZD4基因突变情况，探讨FZD4基因缺陷的临床特征。方法：对24例FEVR先证者(18例家族性和6例散发性)及其部分家系进行FZD4基因外显子直接测序。结果：在4名家族性FEVR患者和1名散发性FEVR患者中发现了4个新的突变。其中3个为错义突变(M105V、R417Q和G488D)，1个为无义突变(W319X)。M105V、R417Q和G488D与该病共分离。在150名健康志愿者的300条染色体中没有发现这些序列变化。尽管FZD4基因突变是FEVR中最常见的视网膜脱离类型，但FZD4基因突变患者的玻璃体视网膜病变的严重程度各不相同。结论：FZD4基因突变存在于部分常染色体显性遗传性和散发性FEVR中。FZD4基因突变是FEVR临床表现多种多样的原因。
Aims: To search for mutations in the frizzled 4 (FZD4) gene in patients with familial exudative vitreoretinopathy (FEVR) and to delineate the defective gene associated clinical features.Methods: Direct sequencing following polymerase chain reaction of exons of FZD4 was performed for 24 probands with FEVR ( 18 familial and six sporadic), and some of their families. Clinical symptoms among individuals with mutations were assessed.Results: Four novel mutations were identified in four patients with familial and one with sporadic FEVR. Three of these mutations were missense ( M105V, R417Q, and G488D) and one was a nonsense change (W319X). M105V, R417Q, and G488D co-segregated with the disease. None of these sequence changes was found among 300 chromosomes from 150 healthy volunteers. The severity of vitreoretinopathy in the individuals involved in this study varied, but no patient with mutations in FZD4 exhibited rhegmatogenous retinal detachment although this pathology is thought to be the most common type of retinal detachment in FEVR.Conclusion: FZD4 gene mutations were found in some cases of autosomal dominant and sporadic FEVR. FZD4 mutations were responsible for FEVR with variable clinical manifestations.