Tian Rong, Wang Shu-Ran, Wang Jing, Chen You-Xin
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China.
Int J Ophthalmol. 2015 Jun 18;8(3):465-9. doi: 10.3980/j.issn.2222-3959.2015.03.06. eCollection 2015.
To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy (BCD) and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD.
Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.
Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations (p.F73L, p.R400H), two splice site mutations (c.802-8_810del17insGC, c.1091-2A>G), and one single base-pair deletion (p.T479TfsX7 or c.1437delC). The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479TfsX7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes.
Mutation c.802-8_810del17insGC and c.1091-2A>G are common mutations in Chinese patients with BCD. Our results expand the allelic heterogeneity of BCD.
分析5例非亲缘关系的中国贝蒂氏结晶性角膜视网膜营养不良（BCD）患者的CYP4V2基因突变情况，并提供这些患者的临床特征。BCD是一种罕见的单基因常染色体隐性遗传性疾病，其特征是视网膜中存在晶体以及视网膜色素上皮萎缩。已发现CYP4V2基因突变是BCD的病因。
对受累个体进行眼科检查。采集外周血样本并提取基因组DNA。用聚合酶链反应扩增CYP4V2基因的所有外显子及其侧翼内含子区域，并通过直接DNA测序筛选突变。还对100条对照染色体进行了筛选以排除非致病性多态性。
眼底检查发现所有患者眼底后极部有微小的淡黄色闪烁晶体以及视网膜色素上皮萎缩。1例患者出现脉络膜新生血管。鉴定出5种不同的CYP4V2突变，包括2种错义突变（p.F73L、p.R400H）、2种剪接位点突变（c.802-8_810del17insGC、c.1091-2A>G）和1种单碱基对缺失（p.T479TfsX7或c.1437delC）。在3例BCD患者中鉴定出2种剪接位点突变。突变p.T479TfsX7是一种新突变，在100条种族匹配的对照染色体中均未观察到。
突变c.802-8_810del17insGC和c.1091-2A>G是中国BCD患者中的常见突变。我们的结果扩展了BCD的等位基因异质性。
