Tian Tian, Zhang Xiang, Zhang Qi, Zhao Peiquan
Department of Ophthalmology, Xinhua Hospital, Affiliated to Medicine School of Shanghai Jiaotong University, Kongjiang Road, Shanghai, China.
Mol Vis. 2019 Feb 7;25:60-69. eCollection 2019.
To identify novel mutations in and to investigate their pathogenicity in a cohort of Chinese patients with familial exudative vitreoretinopathy (FEVR).
Next-generation sequencing was performed in patients with a clinical diagnosis of FEVR. Wide-field angiography was performed in probands and family members if available. Clinical data were collected from patient charts. The effect of the mutations in on its biologic activity in the Norrin/β-catenin signaling pathway was analyzed with the luciferase reporter assay.
Four novel mutations in (c.1188_1192del/p.F396fs, c.1220delC/p.A407Vfs*24, c.905G>A/p.C302Y, c.1325T>A/p.V442E) were identified in four unrelated families. The mutations were not detected in 200 healthy individuals. The variability of the ocular phenotypes was not only observed in the probands and parents harboring the same mutation but also between two eyes in one individual. All four novel mutations introduced reduction in luciferase activity. Compared with the wild-type, the FZD4 level of the four mutants also decreased variably.
Four novel mutations in were identified in Chinese patients with FEVR. No correlation in the reduced luciferase activity and the ocular phenotype was observed in this study. This study further emphasized the complexity of the FEVR-causing machinery.
鉴定[相关基因]的新突变，并在一组中国家族性渗出性玻璃体视网膜病变（FEVR）患者中研究其致病性。
对临床诊断为FEVR的患者进行二代测序。如有可能，对先证者及其家庭成员进行广域血管造影。从患者病历中收集临床数据。用荧光素酶报告基因检测分析[相关基因]突变对Norrin/β-连环蛋白信号通路中其生物学活性的影响。
在四个无关家庭中鉴定出[相关基因]的四个新突变（c.1188_1192del/p.F396fs、c.1220delC/p.A407Vfs*24、c.905G>A/p.C302Y、c.1325T>A/p.V442E）。在200名健康个体中未检测到这些突变。不仅在先证者和携带相同突变的父母中观察到眼部表型的变异性，而且在同一个体的两只眼睛之间也观察到这种变异性。所有四个新突变均导致荧光素酶活性降低。与野生型相比，四个突变体的FZD4水平也有不同程度的下降。
在中国FEVR患者中鉴定出[相关基因]的四个新突变。本研究未观察到荧光素酶活性降低与眼部表型之间的相关性。本研究进一步强调了导致FEVR机制的复杂性。
