Progress in mechanism of CYP4V2 gene mutations for Bietti crystalline corneoretinal dystrophy

Abstract

Bietti crystalline corneoretinal dystrophy (BCD) is a common form of hereditary retinal degeneration in Chinese.Mutation of the cytochrome P450 4V2 (CYP4V2) gene,a novel family member of the cytochrome P450 genes on chromosome 4q35,has been identified in BCD patients,with the common mutation locus at c.802-8 _ 810dell7insGC (Exon7del),c.992A ＞ C (p.H331 P) and c.1091-2A ＞ G (Exon 9del).CYP4V2 is responsible for oxidation of various substrates in the metabolic pathway,especially ω-hydroxylase activity towards ω-3 polyunsaturated fatty acids (PUFAs).CYP4V2 appears to be the only CYP4 memeber at significant levels in retinal cells,and it may be a prominent contributor to local metabolism of PUFAs,mainly DHA (C22:6n-3),in retinal cells.To understand and investigate the main mechanism of CYP4V2 gene mutation causing BCD is important in the study of genetic diagnosis and genetic management of BCD.This review summarized the current advance in the genetic mechanism of BCD and function of CYP4V2 gene,elucidated the substrate specificity and unraveled the biochemical pathways that may impact function of CYP4V2 in BCD patients. Key words: Bietti crystalline corneoretinal dystrophy; Cytochrome P450 enzyme system/genetics; DNA mutation; Lipid metabolism; Retinal diseases/genetics