Abstract: 【Abstract】 Objective  To investigate the genotype and phenotypic features of FZD4 mutations in Chinese familial exudative vitroretinopathy (FEVR) patients. Design Experimental study. Participants Fifty-one Chinese patients with FEVR and 100 unrelated control subjects were recruited and complete ophthalmic examinations performed. Method The coding regions of FZD4 gene was screened for mutations by polymerase chain reaction and direct sequencing. Multiple sequence alignment was conducted to evaluate the conservancy of residues among different FZD4 homologs and human frizzled family. Genotype-phenotype correlations were also analyzed. Main Outcome Measures Gene sequences. Results Totally twelve putative disease-causing mutations were identified, nine of them novel: one deletion (P14fsX57), one nonsense mutations (S491X) and seven missense mutations (G22E, E180K, T237R, R253C, F328S, A339T and D470N). Three reported FZD4 mutations were also detected: H69Y, M105V and W496X. Remarkably, two patients, who harbored compound heterozygous mutations (H69Y with E180K or W496X), had a more severe ocular phenotype than carriers of single H69Y mutation. Conclusion FZD4 mutations were responsible for 29.4% (15/51) of Chinese FEVR patients in this study, similar to other ethnic groups. This study supported the highly polymorphic nature of FZD4 with a differential mutation profile in the Chinese population. The profile of the mutations obtained in FZD4 gene further illustrated the complexity of FEVR and provided a better understanding on the genotype–phenotype correlations. (Ophthalmol CHN, 2013, 22: 224-229)

Key words: familial exudative vitreoretinopathy, FZD4, mutations