Characterization of Bietti's Crystalline Dystrophy Patients With CYP4V2 Mutations

Abstract

Abstract: : Purpose: Mutations in CYP4V2, a member of the cytochrome P450 genes on chromosome 4q35, have recently been found in patients with Bietti's crystalline dystrophy(BCD). The aims of our study were to expand the spectrum of mutations in this gene by screening our series of patients with BCD and to characterize their phenotype. Methods: Seven Chinese patients with clinically diagnosed BCD were identified and recruited into the study. The 11 exons of the CYP4V2 gene were amplified via polymerase chain reaction and were then sequenced and analysed on an ABI PRISM 3100 Genetic Analyser. Detailed characterization of the patients' phenotype was performed with fundal photography, visual field testing, fundal fluorescein angiography and electroretinography. Results: Several mutations and polymorphisms in CYP4V2 were identified in our series of patients. The pathogenic mutations included two novel(S482X and K386T) and the recently reported 15bp deletion that include the 3' splice site for exon 7. A patient with the homozygous 15bp deletion in exon 7 seemed to be associated with a more severe form of BCD, with a more rapid progression of retinal degeneration characterized by glistening intra–retinal crystals, numerous perivascular pigment clumps, widespread chorioretinal atrophy and macular scarring affecting central vision. Conclusions: We have identified novel mutations in the CYP4V2 gene as a cause of Bietti's crystalline dystrophy. Phenotypic characterization of our patients with BCD shows possible correlation with progression and severity of BCD with the mutations identified.

Keywords: mutations • retinal degenerations: hereditary • genetics