title: Identification and population history of CYP4V2 mutations in patients with Bietti crystalline corneoretinal dystrophy.
abstract: To identify known and novel CYP4V2 mutations in patients with Bietti crystalline cornea (BCD), expand the spectrum of CYP4V2 mutations, and characterize the population history of the c.802-8_810del17insGC mutation common in Asian populations, genomic DNA was isolated from peripheral blood samples from 58 unrelated patients with clinical diagnoses of BCD. Exons and flanking intronic regions of the CYP4V2 gene were dideoxy DNA sequenced. Nonpathogenic polymorphisms were excluded and known mutations were identified by sequencing 192 unaffected individuals from similar ethnic backgrounds and examination of online databases. The age of the c.802-8_810del17insGC mutation was estimated using three independent approaches. A total of 28 CYP4V2 mutations, 9 of which were novel, were detected in the 58 patients with BCD. These included 19 missense, 4 nonsense, 2 deletion, 2 splice site, and 1 insertion-deletion mutations. Two missense variants of uncertain significance were also detected. The age of the c.802-8_810del17insGC mutation was estimated to be 1040-8200 generations in the Chinese and 300-1100 generations in the Japanese populations. These results expand the mutation spectrum of CYP4V2, and provide insight into the origin of the c.802-8_810del17insGC mutation in the Chinese population and its transmission to the Japanese population.
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD, USA.
authors.forename: Anren
authors.initials: A
authors.lastname: Li
authors.affiliation: Division of Ophthalmic Genetics, The Eye Hospital of Wenzhou Medical University, China.
authors.forename: Zi-Bing
authors.identifier: 0000-0003-0515-698X
authors.initials: ZB
authors.lastname: Jin
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD, USA.
authors.forename: Xinjing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Center for Retinal Degenerations and Ophthalmic Genetic Diseases, Duke Eye Center, Duke University Medical Center, Durham, NC, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannaccone
authors.affiliation: Center for Genetic Eye Diseases and Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.affiliation: Stein Eye Institute and the UCLA Departments of Ophthalmology and Human Genetics, Los Angeles, CA, USA.
authors.forename: Michael B
authors.identifier: 0000-0001-9498-7982
authors.initials: MB
authors.lastname: Gorin
authors.affiliation: Eye Clinic, University of Campania L Vanvitelli, Caserta CE, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD, USA.
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
mesh_terms: D018912:Arabs / Q000235:genetics; D001213:Asian / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000208:ethnology / Q000235:genetics*; D000072470:Cytochrome P450 Family 4 / Q000235:genetics*; D005091:Exons; D006801:Humans; D009154:Mutation; D010375:Pedigree; D012164:Retinal Diseases / Q000208:ethnology / Q000235:genetics*
chemical_list: C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4