Molecular analysis and phenotypic study in 14 Chinese families with Bietti crystalline dystrophy

• Published in: PloS one 2014-04, Vol.9 (4), p.e94960-e94960
• Main Authors: Yin, Houfa, Jin, Chongfei, Fang, Xiaoyun, Miao, Qi, Zhao, Yingying, Chen, Zhiqing, Su, Zhaoan, Ye, Panpan, Wang, Yao, Yin, Jinfu
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Analysis; Asian Continental Ancestry Group - genetics; Biology and Life Sciences; China; Choroidal Neovascularization - ethnology; Choroidal Neovascularization - genetics; Cornea; Corneal Dystrophies, Hereditary - ethnology; Corneal Dystrophies, Hereditary - genetics; Crystal structure; Crystallinity; Cytochrome; Cytochrome P-450; Cytochrome P-450 Enzyme System - genetics; Cytochrome P450; Cytochrome P450 Family 4; Deoxyribonucleic acid; DNA; DNA Mutational Analysis; Dystrophy; Exons; Family Health; Fatty acids; Female; Gene mutations; Genes; Genetic Association Studies - methods; Genotype; Genotype & phenotype; Hospitals; Humans; Laboratories; Lipids; Male; Medicine; Medicine and Health Sciences; Metabolism; Middle Aged; Molecular Sequence Data; Mutation; Mutation, Missense; Neovascularization; Patients; Pedigree; Phenotype; Polymerase Chain Reaction; Retinal Diseases - ethnology; Retinal Diseases - genetics; Sequence Homology, Amino Acid; Tissue inhibitor of metalloproteinase 3; Tomography; Vascularization; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0094960

To investigate the clinical features and cytochrome P450 family 4 subfamily V polypeptide 2 (CYP4V2) gene mutations in 14 Chinese families with Bietti crystalline dystrophy (BCD). Seventeen patients from 14 unrelated Chinese families with BCD were recruited for complete clinical ophthalmic examination and genetic study. The 11 exons of CYP4V2 were amplified from genomic DNA of all patients and their family members by polymerase chain reaction (PCR) and then sequenced. Exons of TIMP3 were also sequenced in BCD patient associated with choroidal neovascularization (CNV). One hundred and seventy unrelated healthy Chinese subjects were screened for mutations in CYP4V2. All 17 patients with BCD had mutations in CYP4V2; one of these mutations was novel (c.219T>A, p.F73L) and four other mutations had been reported. The p.F73L mutation was a commonly detected mutation in our study (seven out of 34 alleles), either in the homozygous state or in the heterozygous state. Among the patients, considerable phenotypic variability was detected, both within and between families. Screening of TIMP3 did not find any mutation in the BCD patient associated with CNV. The novel CYP4V2 c.219T>A (p.F73L) mutation may be another recurrent mutation in Chinese patients with BCD. Our study expands the mutation spectrum of CYP4V2 and characterizes novel genotype-phenotype associations in Chinese patients with BCD.