Sequence variations of GRM6 in patients with high myopia

[摘要] Purpose: Mutations in the glutamatereceptor metabotropic 6 gene (GRM6) have been identified inpatients with congenital stationary night blindness (CSNB1B). Highmyopia is usually observed in CSNB1B patients. This study tested if anymutations in GRM6 were solely responsible for high myopia. Methods: DNA was prepared from thevenous leukocytes of 96 Chinese patients with high myopia (refractionof spherical equivalent of at least −6.00 diopters [D]) and 96 controls(refraction of spherical equivalent between −0.50 D and +2.00 D withnormal visual acuity). The coding regions and adjacent intronicsequence of GRM6 were amplified by a polymerase chain reaction(PCR) and then analyzed by cycle sequencing. Detected variations wereevaluated in normal controls by heteroduplex-single-strand-conformation(SSCP) polymorphism analysis or restriction fragment polymorphism(RFLP). Results: Four novel variations predictedto 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 96controls. In addition, five rare variations—(c.72G>A,c.504+10g>t, c.726-50g>c, c.1359C>T, and c.1383C>T)—and onecommon variation (c.2437-6g>a) without predicted functionalconsequences and nine known single nucleotide polymorphisms (SNPs) werealso detected. Conclusion: Three novel variations withpotential functional consequences were identified in the GRM6of patients with high myopia, suggesting a potential role in thedevelopment of myopia in rare cases.

[学科分类] 生物化学/生物物理