Genotype and Long-term Clinical Course of Bietti Crystalline Dystrophy in Korean and Japanese Patients

Ophthalmol Retina. 2021 Dec;5(12):1269-1279. doi: 10.1016/j.oret.2021.02.009. Epub 2021 Feb 23.

Abstract

Purpose: To investigate the genotype and long-term clinical phenotype of patients with Bietti crystalline dystrophy (BCD) in Korea and Japan.

Design: Retrospective case series.

Participants: We analyzed 62 patients with clinical features of BCD who harbor pathogenic biallelic CYP4V2 variants in their homozygote or compound heterozygote.

Methods: Data were collected from patient charts, including age, best-corrected visual acuity (BCVA), Goldmann perimetry results, fundus photography, OCT findings, fundus autofluorescence results, and electroretinography findings. We compared the clinical course of the patients with homozygous c.802-8_810de117insGC [exon7del], the most common mutation in the East Asian population, with those of the patients with other genotypes.

Main outcome measures: Best-corrected visual acuity, visual field (VF), and their changes during follow-up.

Results: The mean age at the first visit was 55.2 years, with a mean follow-up of 7.1 years. The mean BCVAs at the first and last visits were 0.28 logarithm of the minimum angle of resolution (logMAR) and 0.89 logMAR, respectively. In genetic testing, c.802-8_810de117insGC was detected in 86 of 124 alleles of the patients, and 36 patients were homozygous for this mutation. The age, BCVA, VF area, central foveal thickness, and abnormal hypoautofluorescent area at either the first or last visit were not different between the exon7del homozygotes and the others. The mean BCVA changes per year were 0.089 logMAR in the exon7del homozygotes and 0.089 logMAR in the others. An age- and gender-adjusted linear regression analysis showed no association between the exon7del homozygote status and the rate of vision loss. Characteristic crystalline deposits in the posterior pole were generally observed in younger patients and disappeared over time along with progressive retinochoroidal atrophy.

Conclusions: Patients with BCD and a homozygote for c.802-8_810de117insGC accounted for more than 50% of this cohort of Korean and Japanese patients, and the clinical effect of this deleterious variant was not severe in the spectrum of CYP4V2 retinopathy.

Keywords: Bietti crystalline dystrophy; CYP4V2; East Asia; Genotype-phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Corneal Dystrophies, Hereditary / diagnosis
  • Corneal Dystrophies, Hereditary / epidemiology
  • Corneal Dystrophies, Hereditary / genetics*
  • Cytochrome P450 Family 4 / genetics*
  • DNA / genetics*
  • DNA Mutational Analysis
  • Electroretinography
  • Female
  • Fluorescein Angiography / methods*
  • Follow-Up Studies
  • Genotype
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • Republic of Korea / epidemiology
  • Retinal Diseases / diagnosis
  • Retinal Diseases / epidemiology
  • Retinal Diseases / genetics*
  • Retrospective Studies
  • Time Factors
  • Tomography, Optical Coherence / methods*

Substances

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

Supplementary concepts

  • Bietti Crystalline Dystrophy