摘要目的 探索P4HA2基因在土家族高度近视人群中的突变情况.方法 收集2015年6月至2017年6月土家族双眼屈光度≥6.0 DS且眼轴长度≥26 mm的高度近视患者288例,对患者行眼科相关检查并采集外周静脉血5 ml,用酚氯仿法抽提患者外周血DNA.通过Sanger测序筛查P4HA2基因可能的致病突变.对于发现的可疑致病突变,均在同地区192例正常人群中进行验证,并通过生物信息学分析预测基因突变的致病性.结果 本研究在288例土家族高度近视患者中共发现4个P4HA2基因突变,包括1个错义突变(c.145C>A)、2个内含子突变(c.1306-62C>T、c.82+22C>T)和1个插入突变(c.179+16_179+17 ins T),其中2个内含子突变及1个插入突变通过在线预测不致病,而错义突变c.145C>A通过Polyphen2在线预测为可疑致病,参照美国ACMG的标准,此变异致病性不确定.结论 P4HA2基因错义突变c.145C>A为土家族高度近视患者可疑致病基因突变.

abstractsObjective To investigate the mutation of P4HA2 gene in Tujia high myopia patients. Methods Clinical data and genomic DNA were collected from 288 Tujia patients with high myopia, whose spherical error ≥-6. 00 diopters and axial length≥26 mm. All coding exons regions of P4HA2 were screened in patients to detect causative mutation by Sanger sequencing. The detected mutation was further screened in 192 normal control chromosomes in the same district. The pathogenicity of genetic mutations was predicted through bioinformatics analysis. This study followed the Declaration of Helsinki. All patients or their guardians signed informed consent. Results Four variations of P4HA2 gene were found in 288 patients,including one missense mutations(c. 145C>A), two in-containing mutations (c. 1306-62C>T,c. 82+22C>T) and one insertion mutation (c. 179+16_179+17 ins T). Missense mutation c. 145C>A was predicted as suspicious pathogenic gene by Polyphen2. According to the standard of ACMG in the United States, the variation was uncertain in pathogenicity. Conclusions Missense mutation c. 145C>A in P4HA2 gene is a suspicious pathogenic gene mutation in Tujia patients with high myopia.