title: Molecular analysis and phenotypic study in 14 Chinese families with Bietti crystalline dystrophy.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Houfa
authors.initials: H
authors.lastname: Yin
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Chongfei
authors.initials: C
authors.lastname: Jin
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Fang
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Miao
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Zhaoan
authors.initials: Z
authors.lastname: Su
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Ye
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors.forename: Jinfu
authors.initials: J
authors.lastname: Yin
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002681:China; D020256:Choroidal Neovascularization / Q000208:ethnology / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000208:ethnology / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000208:ethnology / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D055815:Young Adult
chemical_list: D003577:Cytochrome P-450 Enzyme System; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4
references.citation: Am J Ophthalmol. 1994 Nov 15;118(5):569-82
references.pmid: 7977570
references.citation: Arch Ophthalmol. 1989 Feb;107(2):213-21
references.pmid: 2783846
references.citation: Retina. 2013 Jul-Aug;33(7):1462-5
references.pmid: 23538577
references.citation: Int Ophthalmol. 2011 Feb;31(1):59-61
references.pmid: 20972604
references.citation: Retina. 2004 Jun;24(3):416-26
references.pmid: 15187665
references.citation: Am J Hum Genet. 2002 Nov;71(5):1251-2
references.pmid: 12452182
references.citation: Graefes Arch Clin Exp Ophthalmol. 2000 Sep;238(9):760-4
references.pmid: 11045344
references.citation: Eye (Lond). 2010 Nov;24(11):1728-9
references.pmid: 20798693
references.citation: Br J Ophthalmol. 2012 Mar;96(3):390-3
references.pmid: 21803923
references.citation: Exp Eye Res. 2012 Sep;102:111-2
references.pmid: 21745470
references.citation: Am J Hum Genet. 2000 Nov;67(5):1309-13
references.pmid: 11001583
references.citation: Retina. 2013 Feb;33(2):429-35
references.pmid: 23023527
references.citation: Case Rep Ophthalmol. 2011 Sep;2(3):296-301
references.pmid: 22087103
references.citation: Ophthalmology. 2014 Jun;121(6):1174-84
references.pmid: 24480711
references.citation: Retin Cases Brief Rep. 2009 Fall;3(4):361-3
references.pmid: 25389847
references.citation: Eye (Lond). 2007 Jun;21(6):839-42
references.pmid: 17173010
references.citation: Ophthalmic Paediatr Genet. 1986 Mar;7(1):9-20
references.pmid: 3703493
references.citation: Mol Vis. 2012;18:1182-8
references.pmid: 22605929
references.citation: Br J Ophthalmol. 2013 Feb;97(2):174-9
references.pmid: 23221965
references.citation: Am J Hum Genet. 2004 May;74(5):817-26
references.pmid: 15042513
references.citation: Mol Pharmacol. 2012 Oct;82(4):679-86
references.pmid: 22772592
references.citation: Invest Ophthalmol Vis Sci. 2013 Jun 14;54(6):4158-66
references.pmid: 23661369
references.citation: Invest Ophthalmol Vis Sci. 2010 Feb;51(2):1092-7
references.pmid: 19797200
references.citation: Ophthalmic Genet. 2011 Jun;32(2):118-21
references.pmid: 21385027
references.citation: Drug Metab Dispos. 2009 Nov;37(11):2119-22
references.pmid: 19661213
references.citation: Curr Opin Ophthalmol. 2011 Sep;22(5):332-9
references.pmid: 21730849
references.citation: Mol Vis. 2011;17:1970-7
references.pmid: 21850171
references.citation: Cornea. 2013 Jul;32(7):1002-8
references.pmid: 23538635
references.citation: Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3812-6
references.pmid: 16186368
references.citation: Nat Genet. 1994 Dec;8(4):352-6
references.pmid: 7894485
references.citation: Arch Ophthalmol. 2009 Dec;127(12):1596-602
references.pmid: 20008714
references.citation: Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5212-20
references.pmid: 17962476
references.citation: Ophthalmic Genet. 1997 Sep;18(3):139-41
references.pmid: 9361311
references.citation: Biochem Biophys Res Commun. 2011 Jun 3;409(2):181-6
references.pmid: 21565171
references.citation: Int Ophthalmol. 2013 Jun;33(3):269-76
references.pmid: 23242590