Identification and population history of CYP4V2 mutations in patients with Bietti crystalline corneoretinal dystrophy
Identification and population history of CYP4V2 mutations in patients with Bietti crystalline corneoretinal dystrophy
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Bietti 结晶性角膜视网膜营养不良患者 CYP4V2 突变的鉴定和群体史
DOI：
10.1038/ejhg.2016.184
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发表时间：
2017-04-01
影响因子：
5.2
通讯作者：
Hejtmancik, J. Fielding
中科院分区：
文献类型：
--
作者：
Jiao, Xiaodong;Li, Anren;Hejtmancik, J. Fielding
为了鉴定Bietti晶体角膜（BCD）患者中已知的和新的CYP4V2突变，扩大CYP4V2突变谱，并表征亚洲人群中常见的c.802-8- 810del17insc突变的群体史，从58例临床诊断为BCD的非相关性患者的外周血样本中分离基因组DNA。对CYP4V2基因的外显子和侧翼内含子区进行双脱氧DNA测序。通过对来自相似种族背景的192名未受影响的个体进行测序和检查在线数据库，排除了非致病性多态性，并确定了已知突变。c.802-8- 810del17insc突变的年龄用三种独立的方法估计。在58例BCD患者中共检测到28个CYP4V2突变，其中9个为新突变。这些突变包括19个错义突变，4个无义突变，2个缺失突变，2个剪接位点突变和1个插入-删除突变。还检测到两个不确定意义的错义变体。c.802-8- 810del17insc突变的年龄估计在中国人群中为1040-8200代，在日本人群中为300-1100代。这些结果扩大了CYP4V2的突变谱，并对中国人群中c. 802-8- 810del17insc突变的起源及其向日本人群的传播提供了深入的了解。
To identify known and novel CYP4V2 mutations in patients with Bietti crystalline cornea (BCD), expand the spectrum of CYP4V2 mutations, and characterize the population history of the c.802-8-810del17insGC mutation common in Asian populations, genomic DNA was isolated from peripheral blood samples from 58 unrelated patients with clinical diagnoses of BCD. Exons and flanking intronic regions of the CYP4V2 gene were dideoxy DNA sequenced. Nonpathogenic polymorphisms were excluded and known mutations were identified by sequencing 192 unaffected individuals from similar ethnic backgrounds and examination of online databases. The age of the c.802-8-810del17insGC mutation was estimated using three independent approaches. A total of 28 CYP4V2 mutations, 9 of which were novel, were detected in the 58 patients with BCD. These included 19 missense, 4 nonsense, 2 deletion, 2 splice site, and 1 insertion-deletion mutations. Two missense variants of uncertain significance were also detected. The age of the c.802-8-810del17insGC mutation was estimated to be 1040-8200 generations in the Chinese and 300-1100 generations in the Japanese populations. These results expand the mutation spectrum of CYP4V2, and provide insight into the origin of the c. 802-8-810del17insGC mutation in the Chinese population and its transmission to the Japanese population.