ABSTRACT

Purpose: To report novel mutations in the FZD4 and LRP5 genes, associated with familial exudative vitreoretinopathy (FEVR), and to correlate with clinical features of 7 FEVR patients.

Methods: In this retrospective case series, 7 patients who had undergone genetic panel testing and carried a diagnosis of FEVR were identified. Comprehensive ophthalmic examination and direct DNA sequencing of FEVR-associated genes were performed in all patients. Identified sequence variants were analyzed in silico.

Results: Eight mutations were identified amongst the 7 patients, that included 4 FZD4 mutations and 4 LRP5 mutations. Four novel mutations were identified, two in FZD4 (c.615delC, p.Y206MfsX34) and (c.964A>T, p.I322F), and two in LRP5 (c.2585A>T, p.D862V) and (c.1412 + 1 G > A, splice donor). A broad phenotypic spectrum was noted and no clear genotypic-phenotypic correlation was observed.

Conclusion: These findings expand the mutation spectrum of FZD4 and LRP5.

摘要

目的：报道FZD4和LRP5基因的新突变，与家族性渗出性玻璃体视网膜病变（FEVR）有关，并与7例FEVR患者的临床特征相关。

方法：在此回顾性病例系列中，确定了7例接受过基因检测和诊断为FEVR的患者。所有患者均进行了全面的眼科检查和与FEVR相关基因的直接DNA测序。在计算机上分析了鉴定出的序列变体。

结果：在7例患者中鉴定出8个突变，其中包括4个FZD4突变和4个LRP5突变。鉴定出四个新颖的​​突变，两个在FZD4（c.615delC，p.Y206MfsX34）和（c.964A> T，p.I322F）中，两个在LRP5（c.2585A> T，p.D862V）和（c。 1412 + 1 G> A，剪接供体）。注意到宽的表型谱，没有观察到明确的基因型-表型相关性。

结论：这些发现扩大了FZD4和LRP5的突变谱。