Purchase this article with an account.
Xiaohui Zhang, Bing Dong, Ke Xu, Yang Li; CYP4V2 mutation hot spot and a founder effect in a cohort of Chinese patients with Bietti’s corneoretinal dystrophy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2529.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Bietti crystalline corneoretinal dystrophy (BCD) is a rare autosomal recessively inherited retinal dystrophy. As a member of cytochrome P450 family, CYP4V2 is the causative gene for BCD patients. The aim of this study was to investigate the mutation spectrum of CYP4V2 gene of BCD patients in China, and to characterize the founder effect of the most common mutation in CYP4V2 gene.
According to guidelines approved by the Beijing Tongren Ethics Committee, probands of 15 unrelated families and 78 sporadic cases were recruited into our study. All coding regions including the exon-intron boundaries of the CYP4V2 gene were amplified by PCR and products were direct sequenced. SNaPshot analysis was performed in 53 BCD patients with c.802-8_810del17insGC mutation and 76 normal controls for intragenic single nucleotide polymorphisms (SNPs) genotype. Difference in haplotype distribution between the patient and control group was tested by Fisher’s exact test.
Phenotype heterogeneity including numerous sparkling crystals scattered over the fundus, retinal pigment epithelium (RPE) atrophy and choriodal sclerosis was present in these patients. Twenty-three pathogenic variations were identified, of which five were novel. Among them the c.802-8_810del17insGC mutation was homozygous in 51.6% (48/93) patients and accounted for 70.4% (131/186) of mutant alleles. The most common missese and splice site mutations were c.992A>C (p.H331P) and c.1091-2A>G, which were found in 5.9% and 4.8% of mutant alleles separately. The haplotype analysis revealed that SNPs within intron 2 to exon 6 co-segregated with the c.802-8_810del17insGC mutation in exon 7 in all 53 patients. The heterozygous carrier frequency of this indel mutation in 403 healthy controls of Chinese population was calculated to be 0.007 (3/403).
The mutation hot spot in Chinese BCD patients was c.802-8_810del17insGC, followed by p.H331P and c.1091-2A>G mutation of CYP4V2 gene. Haplotype analysis indicated a founder effect of the c.802-8_810del17insGC mutation in Chinese patients with BCD.
This PDF is available to Subscribers Only