Identification of CYP4V2 mutation in 36 Chinese families with Bietti crystalline corneoretinal dystrophy

Exp Eye Res. 2016 May:146:154-162. doi: 10.1016/j.exer.2016.03.007. Epub 2016 Mar 10.

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.

Keywords: Autosomal recessive; Bietti crystalline corneoretinal dystrophy; CYP4V2; Chinese; Lipid metabolism; Mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • China / epidemiology
  • Corneal Dystrophies, Hereditary / epidemiology
  • Corneal Dystrophies, Hereditary / genetics*
  • Corneal Dystrophies, Hereditary / metabolism
  • Cytochrome P450 Family 4 / genetics*
  • Cytochrome P450 Family 4 / metabolism
  • DNA / genetics*
  • DNA Mutational Analysis
  • Exons
  • Family
  • Female
  • Genetic Testing
  • Genotype
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • Retinal Diseases / epidemiology
  • Retinal Diseases / genetics*
  • Retinal Diseases / metabolism
  • Young Adult

Substances

  • DNA
  • CYP4V2 protein, human
  • Cytochrome P450 Family 4

Supplementary concepts

  • Bietti Crystalline Dystrophy