Novel Frizzled-4 Gene Mutations in Chinese Patients With Familial Exudative Vitreoretinopathy
| Autor: | Wen-Zhen Yu, Li-Yun Jia, Wo-tan Zeng, Chen Liang, Xiaoxin Li |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male China Adolescent Eye Diseases Genotype FZD4 DNA Mutational Analysis Molecular Sequence Data Nonsense mutation Gene mutation Compound heterozygosity medicine.disease_cause Polymerase Chain Reaction Receptors G-Protein-Coupled Young Adult Asian People Retinal Diseases medicine Humans Missense mutation Amino Acid Sequence Child Gene Genetics Mutation business.industry Infant Exudates and Transudates medicine.disease Frizzled Receptors Pedigree Vitreous Body Ophthalmology Phenotype Child Preschool Familial exudative vitreoretinopathy Female business |
| Zdroj: | Archives of Ophthalmology. 128:1341 |
| ISSN: | 0003-9950 |
| Popis: | Objectives To search for mutations in the Frizzled-4 gene ( FZD4 ) in Chinese patients with familial exudative vitreoretinopathy (FEVR) and to delineate the mutation-associated clinical features. Methods Forty-eight Chinese patients with FEVR and 100 unrelated control subjects were recruited and had complete ophthalmic examinations performed. The coding regions of FZD4 were screened for mutations by polymerase chain reaction and direct sequencing. Multiple sequence alignment was conducted to evaluate the conservation of residues among different FZD4 homologs and the human Frizzled family. Genotype-phenotype correlations were also analyzed. Results Twelve putative disease-causing mutations were identified in total, 9 of which were novel: 1 deletion (P14fsX57), 1 nonsense mutation (S491X), and 7 missense mutations (G22E, E180K, T237R, R253C, F328S, A339T, and D470N). Three reported FZD4 mutations were also detected: H69Y, M105V, and W496X. Remarkably, 2 patients who harbored compound heterozygous mutations (H69Y with E180K or W496X) had a more severe ocular phenotype than carriers of a single H69Y mutation. Conclusions FZD4 mutations were responsible for FEVR in 15 of 48 Chinese patients (31.3%) in this study, similar to other ethnic groups. This study supports the highly polymorphic nature of FZD4 with a differential mutation profile in the Chinese population. Clinical Relevance The profile of the mutations obtained in FZD4 further illustrates the complexity of FEVR and provides a better understanding of the genotype-phenotype correlations. |
| Databáze: | OpenAIRE |
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