我国东北地区两家系原发性开角型青光眼的OPTN基因新突变研究

Study of novel mutation of OPTN gene in two primary open angle glaucoma families in Northeast China

目的研究我国东北地区两家系原发性开角型青光眼（POAG）的致病基因并确定其基因突变位点。方法病例对照实验。对两家系POAG患者进行临床研究和系谱分析。采集L家系6例患者和6例健康成员与C家系4例患者和4例健康成员的静脉血，提取基因组DNA。通过连锁分析，确定致病基因的染色体位点后，应用聚合酶链反应（PCR）扩增OPTN基因外显子，直接测序确定致病的基因突变位点。结果L家系POAG患者的OPTN基因第10外显子发生错义突变，1274位点AAA变为GAA，对应的赖氨酸替换为谷氨酸（Lys322Glu）。L家系中健康成员、C家系全部成员及87名正常人均未发现该位点突变。结论OPTN基因新突变（Lys322Glu）是L家系POAG的致病基因。

Objective To identify the mutation gene of two Chinese families with primary open angle glaucoma. Methods It was a case control study. Clinical observation and pedigree analysis were undertaken in two families with primary open angle glaucoma. Venous blood were drawn from 6 affected and 6 unaffected subjects in family L, and from 4 affected and 4 unaffected subjects in family C. Genomic DNA was extracted. Linkage to OPTN gene locus was determined. Mutation of this gene was screened by PCR of OPTN gene exons and direct sequencing. Resdts A missense mutation A1274G in exon 10 of OPTN gene was identified in affected members of family L. The corresponding amino acid change was Lys322Glu. This mutation was not found in unaffected family members of family L, all members of family C and 87 unrelated normal controls. Conclusion A novel mutation of OPTN gene with Lys322Glu change is responsible for the occurrence of primary open angle glaucoma in a Chinese family.