An In-Depth Single-Gene Worldwide Carrier Frequency and Genetic Prevalence Analysis of CYP4V2 as the Cause of Bietti Crystalline Dystrophy.
Transl Vis Sci Technol
; 12(2): 27, 2023 02 01.
Article
in En
| MEDLINE
| ID: mdl-36795063
ABSTRACT
Conclusions:
Our analysis estimates BCD prevalence and revealed large differences among various populations. Moreover, it highlights advantages and limitations of the gnomAD database.Methods:
CYP4V2 gnomAD data and reported mutations were used to calculate carrier frequency of each variant. An evolutionary-based sliding window analysis was used to detect conserved protein regions. Potential exonic splicing enhancers (ESEs) were identified using ESEfinder.Purpose:
Bietti crystalline dystrophy (BCD) is a rare monogenic autosomal recessive (AR) chorioretinal degenerative disease caused by biallelic mutations in CYP4V2. The aim of the current study was to perform an in-depth calculation of worldwide carrier frequency and genetic prevalence of BCD using gnomAD data and comprehensive literature CYP4V2 analysis.Results:
We identified 1171 CYP4V2 variants, 156 of which were considered pathogenic, including 108 reported in patients with BCD. Carrier frequency and genetic prevalence calculations confirmed that BCD is more common in the East Asian population, with â¼19 million healthy carriers and 52,000 individuals who carry biallelic CYP4V2 mutations and are expected to be affected. Additionally, we generated BCD prevalence estimates of other populations, including African, European, Finnish, Latino, and South Asian. Worldwide, the estimated overall carrier frequency of CYP4V2 mutation is 1210, and therefore, â¼37 million individuals are expected to be healthy carriers of a CYP4V2 mutation. The estimated genetic prevalence of BCD is about 1116,000, and we predict that â¼67,000 individuals are affected with BCD worldwide. Translational Relevance This analysis is likely to have important implications for genetic counseling in each studied population and for developing clinical trials for potential BCD treatments.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retinal Diseases
/
Corneal Dystrophies, Hereditary
/
Cytochrome P450 Family 4
Type of study:
Prevalence_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Transl Vis Sci Technol
Year:
2023
Document type:
Article
Affiliation country: