ObjectiveTo investigate the clinical and genetic mutation characteristics of a pedigree with familial exudative vitreoretinopathy (FEVR) associated with a LRP5 gene mutation.

MethodsA pedigree investigation was performed in a two-generation Chinese Han family with FEVR, which was diagnosed in The First Affiliated Hospital of Xi'an Jiaotong University.Three family members, the proband and his parents, underwent ophthalmic examination, including visual acuity, intraocular pressure, slit-lamp microscopy, fundoscopy and wild-field fundus fluorescein angiography (FFA), to clinically characterize the FEVR phenotype.Peripheral blood of the families were collected for high-throughput sequencing and bioinformatics analysis to identify the pathogenic gene.Sanger sequencing verification was conducted for the detected mutation.The pathogenicity of identified mutations was analyzed according to the guidelines of the American Association of Medical Genetics (ACMG) with software such as Mutation Taster, Polyphen-2, PROVEN and REVEL.This study adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The First Affiliated Hospital of Xi'an Jiaotong University (No.2017-740). Written informed consent was obtained from each subject.

ResultsThe proband was a 27-year-old male.Uncorrected visual acuity (UCVA) was 1.0 for his right eye and 1.2 for his left eye.Fundoscopy showed vascular tortuosity and vasodilation in the temporal peripheral retina of both eyes.FFA indicated that hairbrush-like vasculature and non-perfusion lesion in peripheral retina.The best-corrected visual acuity (BCVA) of the proband's mother, a 51-year old female, was 1.0 for the both eyes.Temporal retinal vascular tortuosity in her left eye was found with fluorescein leakage detected by FFA.The BCVA of the proband's father, a 56-year-old male, was 1.0 for both eyes.Leopard fundus and optic disc atrophy were visible.FFA result was normal.The result of genetic test showed that there were two novel gene mutations in the family with LRP5 gene c. 4110T>G(p.Cys1370Trp) and FSCN2 gene c. 1495G>A(p.Gly499Ser). According to guidelines of ACMG, LPR5 c. 4110T>G was a mutation with uncertain significance.Multiple software, such as MutationTaster, Polyphen-2, PROVEN and REVEL predicted that LRP5 c. 4110T>G mutation might cause detrimental effects on genes or gene products.REVEL scale was 0.93, which indicated that it might be a pathogenic variant.

Conclusions LRP5 gene c. 4110T>G(p.Cys1370Trp) may be a novel mutation for FEVR, which enriches the mutation spectrum of LRP5 gene.