title: Novel mutations in FZD4 and phenotype-genotype correlation in Chinese patients with familial exudative vitreoretinopathy.
abstract: To identify novel mutations in the frizzled 4 (FZD4) gene in patients with familial exudative vitreoretinopathy (FEVR) in southern China and to delineate the mutation-associated clinical manifestations.
  
  
  
  Clinical data and genomic DNA were collected from 100 probands and their family members. The coding regions of FZD4 were screened for mutations with PCR and Sanger sequencing. Cosegregation analysis was used to verify suspected variants, and clinical symptoms in the probands were analyzed.
  
  
  
  Fourteen causative heterozygous mutations in FZD4 in 21 unrelated probands were noted, in 21.0% of the index patients (21/100). Four novel missense mutations (C45R, C45S, C53S, and C90R) and three novel deletion mutations (T326fsX356, G492fsX512, and S345_A351del) with a high possibility of pathogenicity were detected. None of these mutations were found in current online databases and 150 ethnically matched control subjects without retinopathy. The majority of the mutations in FZD4 were identified in probands with retinal folds (15/21) and ectopic macula (5/21). No mutations in FZD4 were found in probands with complete tractional retinal detachment in infancy or with mild asymptomatic FEVR in adulthood.
  
  
  
  Seven novel mutations found in this study have broadened the spectrum of mutations in FZD4 known to cause FEVR, providing a deeper understanding of this disease. The results show that mutations in FZD4 are associated with the phenotypes of retinal folds or ectopic macula in FEVR but might not be associated with extreme severe bilateral FEVR during infancy, at least in southern Chinese patients.
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Andina
authors.initials: A
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Miner
authors.initials: M
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Zongyi
authors.initials: Z
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Zijing
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, Guangdong, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary; D000080345:Familial Exudative Vitreoretinopathies; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics*; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: C402930:FZD4 protein, human; D051157:Frizzled Receptors