原发性开角型青光眼一家系致病位点筛查

The screening of pathogenic locus in a primary open angle glaucoma pedigree

目的筛查原发性开角型青光眼POAG一家系的基因致病位点，为POAG的分子遗传学研究提供依据。方法于2005年1—8月在四川省人民医院纳入POAG一个家系，详细收集病史及临床资料，采用国际通用的全基因组扫描技术对家系成员进行全基因组扫描，应用国际公认的遗传连锁分析方法，根据等位基因（单倍体）分型结果，应用两点法分别计算短串联重复序列（STR）标志物的LOD值，以最大LOD值确定阳性位点。结果该家系共4代35名成员，患病者18例，表型正常者17人。患者属于青少年型开角型青光眼，均可见视盘损害和典型视野缺损。患者在儿童时期均有不同程度的双眼视力减退及视野缺损，视功能损伤比较严重。2号染色体上有3个STR标志物LOD值均大于3.0： D2S2369（LOD值4.003 3）、D2S2332（LOD值3.840 2）、D2S337（LOD值4.752 0）。该家系在这3个遗传标志物附近有遗传连锁。该家系阳性位点定位在15号染色体短臂到16号染色体短臂2区，遗传距离约为9 Mb，位于标志物D2S2369和D2S2397之间。结论GLC1H为该POAG大家系的遗传连锁位点，为中国汉族POAG发病机制的研究提供了依据。

ObjectiveTo screen the pathogenic locus and gene in a primary open angle glaucoma（POAG）, and to provide a basis for molecular genetic study of POAG.MethodsA POAG pedigree with 35 members was diagnosed in Sichuan peoples＇ Hospital from January to August 2005.The disease history and clinical data were collected.Genome-wide scan was performed for the families.Specific software was used to calculate the LOD value, which based on the allele （haploid） typing result with two-point method to definite the positive loci by the largest LOD value.ResultsThe POAG family had 35 members of 4 generations.18 patients were diagnosed as juvenile open angle glaucoma from visual disc shape abnormality and loss of typical visual field.All of the patients in this family suffered various degrees of binocular vision loss and vision loss in childhood, with poorly visual function.The LOD values of 3 short tandom repeat （STR） markers on chromosome 2 were greater than 3.0, they were D2S2369 （LOD value 4.003 3）, D2S2332 （LOD value 3.840 2） and D2S337 （LOD value 4.752 0）. There was a genetic linkage near the three genetic markers in the family.The primary glaucoma positive locus was a in chromosome p15 to chromosome p16.2, and the genetic distance was about 9 Mb, locating in between the markers D2S2369 and D2S2397.ConclusionsGLCIH is a pathogenic locus for this POAG pedigree, which supplies an evidence for elucidating the pathogenesis of POAG.