原发性开角型青光眼家系中一个新的MYOC基因突变

New mutation of MYOC gene in a Chinese primary open angle glaucoma family

目的对MYOC(Mycolin)基因突变与一个POAG(primary open-angle glaucoma)家系的相关性进行研究,以便进一步揭示MYOC基因突变在中国人群POAG发病中的作用。方法用PCR-RFLP和基因测序的方法对一个来自中国西部地区POAG家系和200例正常人进行MYOC基因突变(包括G34C,C1009G,A1036G,G1099A,A1139C,T1430A和C1441A等)筛查,同时对检测到的突变结果进行生物信息学分析。结果该家系共67人尚健在56人,其中11人已确诊为POAG,3例因为眼压(IOP)>22mmHg而被定义为可疑者,其余42例表型正常。检出1个新的杂合子突变C38T,该突变存在于4例已确诊的POAG病人和1例可疑者中,突变率为8.8%,200例对照者中未检出。未检出其他突变。结论通过生物信息学分析,虽然C38T突变并未导致蛋白质的结构和性质发生明显变化,但仍不能排除它是该家系的致病性突变的可能。基因检查可能是家族性POAG早期诊断的一种有效的方法。

[Objective] To explore whether the MYOC genetic variants were contribute to the susceptibility for POAG in a Chinese family. [Method] We screened myocilin （MYOC） for mutations （including G34C, C1009G, A1036G,G1099A,Al139C,T1430A and C1441A） in a POAG family by PCR restriction fragment length polymorphism （PCR-RFLP） analysis and DNA sequencing, and 200 matched healthy controls were recruited. Biological softwares were used to analyze the corresponding proteins for detected mutations[Result] The studied pedigree con- taining 56 family members, 11 of them were patients with POAG, 2 were suspects because of their IOP higher than 22mmHg, and the rest were asymptomatic. A homoplastic C38T, for the first time, was found in 4 of 11 patients and in lof the 3 suspects. The frequency of C38T was 8.8%, and not found in 200 controls. G34C, C1009G,A1036G, G1099A, A1139C, T1430A and C1441A mutations were not detected. [ Conclusion ] Secondary structure prediction revealed that there were not obvious conformational changes in C38T mutant of MYOC versus wild type, but we still can not exclude it providing additional clues to the disease pathogenesis. DNA testing for people at high risk of developing glaucoma may be beneficial, especially in early onset type of glaucoma pedigrees.