Identification of CYP4V2 mutation in 36 Chinese families with Bietti crystalline corneoretinal dystrophy. (May 2016)

• Record Type: Journal Article
• Authors: Yin, Xiaobei; Yang, Liping; Chen, Ningning; Cui, Hui; Zhao, Lin; Feng, Lina; Li, Aijun; Zhang, Huirong; Ma, Zhizhong; Li, Genlin
• Is Part Of: Experimental eye research. Volume 146(2016:May)
• Page Start: 154
• Page End: 162
• Publication Date: 2016-05
• Subjects: CYP4V2 -- Bietti crystalline corneoretinal dystrophy -- Autosomal recessive -- Mutation -- Lipid metabolism -- Chinese; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2016.03.007
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Bietti crystalline corneoretinal dystrophy (BCD) is an inherited eye disease that is most common in the Chinese. It is caused by a mutation in the CYP4V2 gene. In this study, 43 Chinese BCD families were recruited; most patients manifested the characteristic phenotype of BCD, with 2 families initially misdiagnosed with retinitis pigmentosa. Five patients in our cohort presented with BCD and choroidal neovascularization (CNV), and 1 patient presented with typical BCD and abnormality in the terminals of both fingers and toes. A total of 17 pathogenic mutations involving 68 alleles were identified from 36 families using targeted exon sequencing and Sanger sequencing; we achieved a diagnostic rate of approximately 84%. Fifteen families were found to carry homozygous mutations, 17 families carried compound heterozygous mutations, and 4 families carried a single heterozygous mutation. Of the mutations identified, four variants c.802-8_810del17bpinsGC, c.802-8_810del17bpinsGT, c.992A > C (p.H331P), and c.1091-2A > G accounted for 71% of the mutations identified in CYP4V2 . These mutations were hotspots in Chinese populations for BCD. Five among them were novel and predicted to be disease-causing, including c.65T > A (p.L22H), c.681_4delTGAG (p.S227Rfs*1), c.802-8_810del17bpinsGT, c.965_7delAAG (p.321delE), and c.994G > A (p.D332N). No apparent correlation between genotype and phenotype was identified. Our findings broaden the spectrum of CYP4V2 mutations that cause BCD and the phenotypic spectrum of the disease in Chinese families. These results will be useful for the genetic diagnosis of BCD, genetic consultation, and gene therapy in the future. Highlights: A total of 17 pathogenic mutations were identified in 36 Chinese BCD families. Four variants account for 71% of the mutation identified, were mutation hotspot. Five novel mutations were identified in CYP4V2 gene. One patient present with BCD and terminal abnormality in both fingers and toes. No apparent correlation between genotype-phenotype was identified.