title: Identification of CYP4V2 mutation in 36 Chinese families with Bietti crystalline corneoretinal dystrophy.
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.
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, PR China.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, PR China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Chen
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, PR China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, PR China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, PR China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, PR China. Electronic address: ligenglin@263.net.
authors.forename: Genlin
authors.initials: G
authors.lastname: Li
mesh_terms: D000328:Adult; D000483:Alleles; D002681:China / Q000453:epidemiology; D003317:Corneal Dystrophies, Hereditary / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000072470:Cytochrome P450 Family 4 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005190:Family; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012164:Retinal Diseases / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004247:DNA; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4
keywords: Autosomal recessive; Bietti crystalline corneoretinal dystrophy; CYP4V2; Chinese; Lipid metabolism; Mutation