Trifan O C, Traboulsi E I, Stoilova D, Alozie I, Nguyen R, Raja S, Sarfarazi M
Surgical Research Center, Department of Surgery, Farmington, Connecticut 06030-1110, USA.
Am J Ophthalmol. 1998 Jul;126(1):17-28. doi: 10.1016/s0002-9394(98)00073-7.
Two genes for adult-onset primary open-angle glaucoma have been mapped to chromosomes 2cen-q13 and 3q21-q24. We studied a family with adult-onset primary open-angle glaucoma in which the disease did not map to these two chromosomal regions.
We ascertained a four-generation family with adult-onset primary open-angle glaucoma in which the disease status of individuals was objectively assigned using defined criteria. Complete ophthalmologic examinations, visual field testing, optic nerve head photographs, and venous blood samples were obtained. Family members were genotyped using polymerase chain reaction amplification of microsatellite polymorphic markers. Linkage analysis was performed and lod scores were calculated. Haplotype transmission data were analyzed.
A total of 20 subjects in three successive generations agreed to participate in the study. This included samples from eight affected subjects, one glaucoma suspect, one normal individual, and two spouses in generations II and III, and an additional eight individuals in generation IV. The phenotype in this family appears to be variable, with onset of visual field loss in middle age, followed by modest elevation of intraocular pressure and progression of the disease in older individuals. Linkage was established with a group of DNA markers located in the 8q23 region. A lod score value of 3.61 was obtained using marker D8S1471. Three other markers from the same region gave lod score values of over 3.0. Haplotype transmission data identified two recombination events that placed the gene in a 6.3-cM region flanked by D8S1830 and D8S592. The disease-bearing haplotype was inherited by eight affected subjects and three glaucoma suspects.
We present evidence for a third adult-onset primary open-angle glaucoma locus (GLC1D) on chromosome 8q23. The genetic heterogeneity of adult-onset glaucoma is evident from the multiplicity of chromosomal loci associated with this disease.
两个与成人型原发性开角型青光眼相关的基因已被定位到2号染色体着丝粒-q13和3号染色体q21-q24区域。我们研究了一个成人型原发性开角型青光眼家族，该家族中疾病并未定位到这两个染色体区域。
我们确定了一个四代的成人型原发性开角型青光眼家族，其中个体的疾病状态通过明确的标准进行客观判定。进行了全面的眼科检查、视野测试、视神经乳头照相，并采集了静脉血样本。使用微卫星多态性标记的聚合酶链反应扩增对家庭成员进行基因分型。进行连锁分析并计算lod值。分析单倍型传递数据。
连续三代共有20名受试者同意参与研究。这包括来自8名患病受试者、1名青光眼疑似患者、1名正常个体以及第二代和第三代中的两名配偶的样本，以及第四代中的另外8名个体。该家族中的表型似乎具有变异性，视野缺损在中年开始出现，随后眼压适度升高，且在老年个体中疾病进展。与位于8q23区域的一组DNA标记建立了连锁关系。使用标记D8S1471获得的lod值为3.61。来自同一区域的其他三个标记的lod值超过3.0。单倍型传递数据确定了两个重组事件，将该基因定位在由D8S1830和D8S592侧翼的6.3厘摩区域内。患病单倍型由8名患病受试者和3名青光眼疑似患者遗传。
我们提供了位于8号染色体q23上的第三个成人型原发性开角型青光眼基因座（GLC1D）的证据。成人型青光眼的遗传异质性从与该疾病相关的多个染色体位点中可见一斑。
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