Bietti Crystalline Corneoretinal Dystrophy Associated with CYP4V2 Gene Mutations

Abstract

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive chorioretinal dystrophy characterized by progressive night blindness, tiny, yellowish, glistening retinal crystals, choroidal sclerosis, and crystalline deposits in the peripheral cornea. Recent studies have demonstrated that the CYP4V2 gene which encodes a CYP450 family protein is the causative gene of the disease. We have identified a homozygous mutation in the CYP4V2 gene in 8 separate Japanese patients with BCD and conclude that mutations in the CYP4V2 gene are the major cause of BCD. The IVS6-8_c.810del/insGC mutation is found at a higher frequency in the Asian populations suggesting a founder effect.

Genetics of Bietti Crystalline Dystrophy

“…49,55 Interestingly, clinical symptoms of BCD remain only in the eyes. The link between altered 32 Yin et al, 36 Meng et al, 59 Manzouri et al, 64 Shan et al 60 15 3 c.332T>C p.I111T Missense Li et al, 55 Astuti et al, 63 Rossi et al, 61 García-García et al, 65 Haddad et al, 66 Rossi et al 67 10 Lin et al, 11 Li et al, 17 Gocho et al, 27 Halford et al, 32 Yin et al, 36 Li et al, 55 Xiao et al, 57 Meng et al, 59 Astuti et al, 63 Nakamura et al, 68 Lee et al, 69 Chung et al, 70 Gekka et al, 71 Jin et al, 72 Liu et al, 73 Shan et al, 60 Tian et al, 62 Wada et al, 74 10 Li et al, 17 Li et al, 55 Xiao et al, 57 Meng et al, 59 36 Meng et al, 59 Mamatha et al 77 43 9 c.1091-2A>G Exon9del Splice site Li et al, 17 Yin et al, 36 Li et al, 55 Xiao et al, 57 Meng et al, 59 Shan et a...…”

Ocular cytochrome P450s and transporters: roles in disease and endobiotic and xenobiotic disposition

“…Since the initial 2004 article, many additional mutations of CYP4V2 have been identified, and currently more than 30 are described (Garcia-Garcia et al, 2013; Gekka et al, 2005; Haddad et al, 2012; Jin et al, 2006; Lee et al, 2005; Li et al, 2004; Lin et al, 2005; Mamatha et al, 2011; Manzouri et al, 2012; Nakamura et al, 2006; Rossi et al, 2011, 2013; Shan et al, 2005; Song et al, 2013; Wada et al, 2005; Wang et al, 2012; Xiao et al, 2011; Yokoi et al, 2010, 2011; Zenteno et al, 2008). As reviewed in Kelly et al (2011), the most common mutation in BCD results in deletion of exon 7.…”

Evolution of Cellular Inclusions in Bietti’s Crystalline Dystrophy

“…To date over 23 CYP4V2 mutations have been reported in BCD cases, the most common being a (IVS6-8delTCATACAGGTCATCGCG/insGC) in Japanese, Chinese and European patients but less commonly in Singapore patients with BCD 25–27,29–33,34,36,37,39. CYP4V2 is composed of 11 exons that that encode a widely expressed 525 amino acid CYP450 family member, which is presumably involved in fatty acid metabolism 27.…”