Recessive Mutations in the CYP4V2 Gene in East Asian and Middle Eastern Patients With Bietti Crytalline Corneoretinal Dystrophy

Abstract

Abstract: : Purpose: Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive chorioretinal dystrophy characterized by tiny yellowish gittering retinal crystals, choroidal sclerosis, and crystals in the peripheral cornea, associated with progressive night blindness. Recently the CYP4V2 gene that encodes a CYP450 family protein was identified as the mutated gene in BCD. The aim of this study is to report mutations of the CYP4V2 gene in East Asian and Middle Eastern patients with BCD and to report the clinical features in the patients. Methods:Eleven unrelated patients with typical clinical features of BCD were examined. Genomic DNA was extracted from peripheral blood leukocytes, and all 11 exons and the flanking intron of the CYP4V2 gene were amplified by polymerase chain reaction and directly sequenced. A complete ophthalmologic examination was performed. Results: We found recessive mutations in the gene in all of the patients. Two novel mutations, L173W and Q450X, were identified in a Japanese patient and two unrelated patients from Middle Eastern countries, respectively. A previously reported mutation IVS6–8_810delinsGC was identified in seven unrelated Japanese patients and a Chinese patient with BCD. All patients shared a characteristic fundus appearance with numerous intraretinal crystal deposits and atrophy of the retinal pigment epithelium. However, the clinical findings including elecroretinogram recordings indicated that there was considerable variation in the degree of visual dysfunction even among patients carrying the same mutation at similar ages, raising the possibility of environmental or additional genetic factors influencing the course of the retinal disease. Conclusions:Most patients with BCD are caused by a CYP4V2 gene mutation. The mutation IVS6–8_810delinsGC may be especially prevalent among BCD patients in East Asian countries, suggesting a founder effect.

Keywords: retinal degenerations: hereditary • mutations • genetics