Richards J E, Lichter P R, Herman S, Hauser E R, Hou Y C, Johnson A T, Boehnke M
Department of Ophthalmology, University of Michigan, Ann Arbor, USA.
Ophthalmology. 1996 Jul;103(7):1035-40. doi: 10.1016/s0161-6420(96)30570-8.
To determine whether an adult-onset variety of primary open-angle glaucoma in family UM:POAG1 is linked to the previously mapped GLC1A juvenile-onset primary open-angle glaucoma locus on chromosome 1q or whether linkage can be excluded.
Microsatellite repeat markers from the 9 cM D1S196 to D1S218 interval containing the GLC1A gene were amplified by polymerase chain reaction from DNA samples collected from 11 members of one sibship in family UM:POAG1. Haplotype analysis was carried out, including calculation of the probability that the observed data would have been obtained if the underlying cause of primary open-angle glaucoma in this family were a defect in a gene located in the tested interval. Linkage analysis was carried out under an autosomal dominant model for GLC1A glaucoma.
In family UM:POAG1, primary open-angle glaucoma was diagnosed in six surviving and one deceased member of a sibship of 13 individuals during the fifth or sixth decade of life. Glaucoma in this family has a later average age at diagnosis and significantly less elevation in intraocular pressure than GLC1A glaucoma so far described. Haplotype analysis, using a population prevalence up to 0.9%, shows that it is unlikely that the reported data would have been observed if primary open-angle glaucoma in this pedigree were due to the GLC1A locus on chromosome 1q21-q31. Linkage analysis under the juvenile glaucoma autosomal dominant model allowed exclusion of linkage across the entire GLC1A genetic inclusion interval, with a maximum lod score in the interval of -3.28.
The most likely interpretation of these observations is that a defect in the GLC1A glaucoma gene is not responsible for adult-onset primary open-angle glaucoma in family UM:POAG1. This suggests the existence of at least two primary open-angle glaucoma genes, the previously reported GLC1A gene on chromosome 1q and another gene located elsewhere in the genome. Diagnosis of UM:POAG1 glaucoma between 42 and 57 years of age also raises questions regarding the relation of the glaucoma present in this family to the common later-age-onset form of the disease.
确定UM:POAG1家族中成人发病型原发性开角型青光眼是否与先前定位在1号染色体上的青少年发病型原发性开角型青光眼基因座GLC1A连锁，或者是否可以排除连锁关系。
从UM:POAG1家族一个同胞组的11名成员采集的DNA样本中，通过聚合酶链反应扩增包含GLC1A基因的9厘摩（cM）D1S196至D1S218区间的微卫星重复标记。进行单倍型分析，包括计算如果该家族原发性开角型青光眼的潜在病因是位于测试区间的基因缺陷时，获得观察数据的概率。在GLC1A青光眼的常染色体显性模型下进行连锁分析。
在UM:POAG1家族中，一个13人同胞组中有6名存活成员和1名已故成员在生命的第五或第六个十年被诊断为原发性开角型青光眼。该家族青光眼的诊断平均年龄较晚，且眼内压升高程度明显低于迄今所描述的GLC1A青光眼。使用高达0.9%的人群患病率进行单倍型分析表明，如果该系谱中的原发性开角型青光眼是由1号染色体q21 - q31上的GLC1A基因座引起的，那么不太可能观察到所报告的数据。在青少年青光眼常染色体显性模型下进行的连锁分析排除了整个GLC1A基因包含区间的连锁关系，该区间的最大对数似然值为 - 3.28。
这些观察结果最可能的解释是，GLC1A青光眼基因缺陷并非UM:POAG1家族中成人发病型原发性开角型青光眼的病因。这表明至少存在两个原发性开角型青光眼基因，即先前报道的1号染色体上的GLC1A基因和基因组其他位置的另一个基因。UM:POAG1青光眼在42至57岁之间被诊断出来，这也引发了关于该家族中存在的青光眼与常见的晚发型疾病形式之间关系的疑问。
