目的：探讨SCO2(OMIM 604272)基因在恩施土家族苗族自治州高度近视患者中的致病性变异。方法：共招募384例高度近视患者，其中至少一眼球镜度数≤-6.00 D，且眼轴长度≥26.00 mm。应用苯酚-氯仿法从5 mL外周静脉血中提取DNA。通过Sanger测序以鉴定SCO2第2外显子的致病性变异。运用计算机预测软件对检测到的变异进行评估。来自同一地区的288名健康人群作为正常对照。结果：共检测出7个突变位点，分别为4个同义突变(c.201C>T/p.=，c.576C>T/p=，c.633A>C/p.=，c.780T>C/p.=.)，2个错义突变(c.187A>G/p.Ile63Val，c.59G>C/p.Arg20Pro)和1个无义突变(c.544C>T/p.Gln182*)。通过PolyPhen2、SIFT和Provean软件预测，两个错义突变没有致病性。新的无义突变(c.544C>T/p.Gln182*)在1000G中未被发现，在288个正常对照中也未被发现。Variant Taster预测该无义突变位点是保守的。结论：新发现的无义突变可能是我们研究的高度近视患者的致病原因。SCO2与高度近视相关，而这批高度近视人群中SCO2基因突变的发生率低至1/384； 该无义突变可能是中国恩施土家族苗族自治州高度近视的一种罕见变异。

AIM: To evaluate the pathogenic variants of the SCO2(OMIM 604272)gene in patients with high myopia from Enshi Tujia and Miao Autonomous Prefecture of China.METHODS: A total of 384 patients with high myopia whose spherical refractive error was ≤ -6.00 D and whose axial length was ≥26.00 mm in at least one eye were recruited. DNA was extracted by the phenol-chloroform method from 5 mL of peripheral venous blood. Sanger sequencing was performed to identify pathogenic variants in exon 2 of SCO2. The detected variants were evaluated via in silico prediction software. A total of 288 people from the same district were included as the normal control cohort.RESULTS: Seven variants were detected, namely, four synonymous variants(c.201C>T/p.=, c.576C>T/p.=, c.633A>C/p.=, c.780T>C/p.=.), two missense variants(c.187A>G/p.Ile63Val, c.59G>C/p.Arg20Pro)and one nonsense variant(c.544C>T/p.Gln182*). The two missense variants were not damaging, as predicted by PolyPhen2, SIFT and Provean. The novel nonsense variant(c.544C>T/p.Gln182*)cannot be found in the 1000 Genomes Project and was not identified in 288 normal controls. Variant Taster suggested that the nonsense variant site was conserved.CONCLUSION: The newly identified nonsense mutation may be responsible for high myopia of the patients in our cohort. SCO2 is associated with high myopia, while the incidence of SCO2 variants in high myopia in this cohort was as low as 1/384; the nonsense mutation may be a scarce variant of high myopia in the Enshi Tujia and Miao Autonomous Prefecture of China.

国家自然科学基金(No.81360154)