色素性青光眼的分子遗传学研究

Great progress has been made in deciphering the molecular mechanism underlying the pathogenesis of certain types of glaucoma, but not pigmentary glaucoma. Therefore, we can only recognize this disease from clinical point of view, but not from molecular level. Our group has worked on molecular genetics of ocular diseases including primary open angle glaucoma for almost 15 years, and this study will focus on pigmentary glaucoma. We have collected 6 pedigrees and 70 sporadic patients with pigmentary glaucoma, and achieved preliminary results based on genetic analysis. The directions of this study include the collection of at least 8 pedigrees and 150 sporadic patients with the help of the multicenter study of glaucoma genetics, determining the genetic defects responsible for the clinical phenotypes via whole exome sequencing technology. This study will help us to understand the molecular basis underlying the pigmentary glaucoma, develop a mutation database that can be used for diagnostic and therapeutic trials.

本课题旨在找出色素性青光眼的致病基因。相对于其他类型的青光眼而言，色素性青光眼的分子遗传学研究进展较为缓慢，使我们对该病的认识还局限于一些临床现象，因此当前亟待从基因水平认识色素性青光眼。课题组多年来在对其它眼遗传病研究取得一定成绩的同时，也一直致力于本病的研究。前期已收集了6个色素性青光眼家系和70个散发病例，并在候选基因筛查及家系分析等方面取得了初步成果。我们已加入有全国各地100余单位参加的全国青光眼遗传多中心协作组并专门负责色素性青光眼的收集和研究。课题组拟采用全外显子组测序等分子遗传学方法寻找色素性青光眼的致病基因。该方法及后续的数据分析整理及验证曾数次被我们成功用于遗传性眼病致病基因的检测工作。本课题有望弥补国内外在该研究领域的不足，同时对开拓本病其它研究领域如早期诊断，预防及基因治疗等有重要意义，使我国在色素性青光眼的研究处于领先水平。

相对于其他类型的青光眼而言，色素性青光眼的分子遗传学研究进展较为缓慢，人类对于该病的认识局限于临床现象，因此当前亟待从基因水平认识色素性青光眼。本课题旨在找出色素性青光眼的致病基因及突变位点。本课题共收集了9个色素性青光眼家系和80例散发病例，通过候选基因测序及全外显子测序技术，最终证实了2个色素性青光眼的致病基因，分别为ANKRD53基因和CPAMD8基因，扩展了色素性青光眼的致病基因谱，为色素性青光眼的发病机制研究以及基因诊断提供依据。为了进一步探究色素性青光眼的发病机制，本课题还针对致病基因突变位点进行功能学研究，从动物学和细胞学的角度对ANKRD53、CPAMD8基因在色素性青光眼发病进程中各项指标进行分子生物学检测。本课题有望弥补国内外在该研究领域的不足，同时对开拓本病其它研究领域如早期诊断，预防及基因治疗等有重要意义，使我国在色素性青光眼的研究处于领先水平。