Xu Xiaoyu, Li Shiqiang, Xiao Xueshan, Wang Panfeng, Guo Xiangming, Zhang Qingjiong
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Mol Vis. 2009 Oct 19;15:2094-100.
Mutations in the glutamate receptor metabotropic 6 gene (GRM6) have been identified in patients with congenital stationary night blindness (CSNB1B). High myopia is usually observed in CSNB1B patients. This study tested if any mutations in GRM6 were solely responsible for high myopia.
DNA was prepared from the venous leukocytes of 96 Chinese patients with high myopia (refraction of spherical equivalent of at least -6.00 diopters [D]) and 96 controls (refraction of spherical equivalent between -0.50 D and +2.00 D with normal visual acuity). The coding regions and adjacent intronic sequence of GRM6 were amplified by a polymerase chain reaction (PCR) and then analyzed by cycle sequencing. Detected variations were evaluated in normal controls by heteroduplex-single-strand-conformation (SSCP) polymorphism analysis or restriction fragment polymorphism (RFLP).
Four novel variations predicted to have potential functional changes were identified: c.67-82delCAGGCGGGCCTGGCGCinsT (p.Gln23_Arg28delinsCys), c.858-5a>g (r.spl?), c.1172G>A (p.Arg391Gln), and c.1537G>A (p.Val513Met). Except for c.1172G>A, the other three were not detected in the 96 controls. In addition, five rare variations-(c.72G>A, c.504+10g>t, c.726-50g>c, c.1359C>T, and c.1383C>T)-and one common variation (c.2437-6g>a) without predicted functional consequences and nine known single nucleotide polymorphisms (SNPs) were also detected.
Three novel variations with potential functional consequences were identified in the GRM6 of patients with high myopia, suggesting a potential role in the development of myopia in rare cases.
在先天性静止性夜盲症（CSNB1B）患者中已鉴定出代谢型谷氨酸受体6基因（GRM6）的突变。CSNB1B患者通常会出现高度近视。本研究测试GRM6中的任何突变是否是高度近视的唯一原因。
从96名中国高度近视患者（等效球镜屈光度至少为-6.00屈光度[D]）和96名对照者（等效球镜屈光度在-0.50 D至+2.00 D之间且视力正常）的静脉白细胞中提取DNA。通过聚合酶链反应（PCR）扩增GRM6的编码区和相邻内含子序列，然后通过循环测序进行分析。通过异源双链-单链构象（SSCP）多态性分析或限制性片段多态性（RFLP）在正常对照中评估检测到的变异。
鉴定出四个预测具有潜在功能变化的新变异：c.67-82delCAGGCGGGCCTGGCGCinsT（p.Gln23_Arg28delinsCys）、c.858-5a>g（r.spl?）、c.1172G>A（p.Arg391Gln）和c.1537G>A（p.Val513Met）。除c.1172G>A外，其他三个变异在96名对照者中未检测到。此外，还检测到五个罕见变异（c.72G>A、c.504+10g>t、c.726-50g>c、c.1359C>T和c.1383C>T）以及一个无预测功能后果的常见变异（c.2437-6g>a）和九个已知的单核苷酸多态性（SNP）。
在高度近视患者的GRM6中鉴定出三个具有潜在功能后果的新变异，提示在罕见情况下对近视发展可能起作用。
