Recessive mutations in the CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystalline corneoretinal dystrophy -: art. no. e38
Recessive mutations in the CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystalline corneoretinal dystrophy -: art. no. e38
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DOI：
10.1136/jmg.2004.029066
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发表时间：
2005-06-01
影响因子：
4
通讯作者：
Miyake, Y
中科院分区：
文献类型：
--
作者：
Lin, J;Nishiguchi, KM;Miyake, Y
背景资料：Bietti结晶性角膜视网膜营养不良（BCD）是一种常染色体隐性遗传性疾病，其特征是微小的黄色闪烁视网膜晶体、脉络膜硬化和周边角膜中的晶体，与进行性夜盲症相关。CYP 4V 2编码细胞色素P450（CYP 450）蛋白家族的一个成员，最近被确定为致病基因。方法：我们招募了11例具有典型临床特征的BCD患者，其中8例为日本人，2例为中东人，1例为中国人。从外周血白细胞中提取基因组DNA，扩增CYP 4V 2基因的所有11个外显子和侧翼内含子剪接位点并测序。结果：11例患者均发现CYP 4V 2基因隐性突变。两个新的突变，L173 W和Q450 X，分别在日本患者和两个无关的患者从中东国家。每个病人都是纯合子。在7名无关的日本患者和1名中国BCD患者中发现了先前报告的突变IVS 6 -8_810delinsGC。所有BCD患者的眼底表现都有特征性的视网膜内晶体沉积和视网膜色素上皮萎缩。然而，临床研究结果，包括elecroretinograph记录，表明，有相当大的差异，即使在年龄相仿的患者携带相同的mutation.Conclusions：缺陷的CYP 4V 2的视觉功能障碍的程度是BCD的主要原因。IVS 6 -8_810delinsGC突变等位基因可能在东亚国家的BCD患者中特别普遍，这是由单一创始人造成的。疾病严重程度的变化表明环境或其他遗传因素影响视网膜疾病的病程。
Background: Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessively inherited disorder characterised by tiny yellowish glittering retinal crystals, choroidal sclerosis, and crystals in the peripheral cornea, associated with progressive night blindness. CYP4V2, encoding a member of cytochrome p450 (CYP450) protein family, was recently identified as the causative gene.Methods: We recruited 11 unrelated patients with BCD and characteristic clinical features; eight of Japanese, two of Middle Eastern, and one of Chinese ancestry. Genomic DNA was extracted from peripheral blood leucocytes, and all 11 exons and the flanking intron splice sites of the CYP4V2 gene were amplified and sequenced. A complete ophthalmological examination was performed.Results: We found recessive mutations in the CYP4V2 gene in all of the 11 patients. Two novel mutations, L173W and Q450X, were identified in a Japanese patient and two unrelated patients from Middle Eastern countries, respectively. Each patient was a homozygote. A previously reported mutation IVS6-8_810delinsGC was identified in seven unrelated Japanese patients and the Chinese patient with BCD. All patients with BCD shared a characteristic fundus appearance with numerous intraretinal crystal deposits and atrophy of the retinal pigment epithelium. However, the clinical findings, including elecroretinograph recordings, indicated that there was considerable variation in the degree of visual dysfunction even among patients of similar ages carrying the same mutation.Conclusions: Defects in CYP4V2 are the main cause of BCD. The IVS6-8_810delinsGC mutant allele may be especially prevalent among patients with BCD in East Asian countries, resulting from a single founder. Variation of disease severity suggests that environmental or additional genetic factors influence the course of the retinal disease.