Craig J E, Baird P N, Healey D L, McNaught A I, McCartney P J, Rait J L, Dickinson J L, Roe L, Fingert J H, Stone E M, Mackey D A
Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.
Ophthalmology. 2001 Sep;108(9):1607-20. doi: 10.1016/s0161-6420(01)00654-6.
To investigate the phenotype and age-related penetrance of primary open-angle glaucoma (POAG) in Australian families with the most common Myocilin mutation (Gln368STOP).
Cross-sectional genetic study.
Eight pedigrees carrying the Gln368STOP mutation were ascertained from 1730 consecutive cases of POAG in the Glaucoma Inheritance Study in Tasmania.
Index cases and available family members were examined for signs of glaucoma, and the presence of the GLC1A Gln368STOP mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing.
From the eight pedigrees, 29 Gln368STOP mutation-carrying individuals with either ocular hypertension (OHT) or POAG were found, with a mean age at diagnosis of 52.4 +/- 12.9 years and a mean peak intraocular pressure (IOP) of 28.4 +/- 4.7 mmHg. A further 11 mutation carriers older than 40 years have been studied, who as yet show no signs of OHT or POAG. Within the 8 pedigrees, a further 31 individuals with OHT or POAG were identified who did not carry the Gln368STOP mutation. For these individuals the mean age at diagnosis was higher (62.3 +/- 13.7 years, P < 0.01), and the mean peak IOP was lower (25.4 +/- 6.4 mmHg, P = 0.01). For Gln368STOP carriers, age-related penetrance for OHT or POAG was 72% at age 40 years and 82% at age 65 years. A positive family history of POAG was present in all index cases. Five of the eight pedigrees had a positive family history on both maternal and paternal sides. Seven of the eight pedigrees had one or more individuals with POAG who did not carry the mutation. Eight of the 29 Gln368STOP carriers with OHT or POAG had undergone trabeculectomy.
The GLC1A Gln368STOP mutation is associated with POAG, which in the pedigrees studied is of a younger age of onset and higher peak IOP than non-mutation glaucoma cases. In addition, Gln368STOP mutation glaucoma cases were more likely to have undergone glaucoma drainage surgery. We have not observed simple autosomal dominant inheritance patterns for POAG in these pedigrees. Other factors, as yet uncharacterized, are involved in expression of the POAG phenotype in Gln368STOP pedigrees.
在澳大利亚患有最常见的肌纤蛋白（Myocilin）突变（Gln368STOP）的家族中，研究原发性开角型青光眼（POAG）的表型及年龄相关外显率。
横断面遗传学研究。
从塔斯马尼亚青光眼遗传研究中连续的1730例POAG病例中确定了8个携带Gln368STOP突变的家系。
对索引病例和可用的家庭成员进行青光眼体征检查，并通过单链构象多态性分析及随后的直接测序确定是否存在GLC1A Gln368STOP突变。
在这8个家系中，发现29名携带Gln368STOP突变且患有高眼压症（OHT）或POAG的个体，诊断时的平均年龄为52.4±12.9岁，平均眼压峰值为28.4±4.7 mmHg。另外对11名年龄超过40岁的突变携带者进行了研究，他们目前尚未表现出OHT或POAG的体征。在这8个家系中，还确定了另外31名患有OHT或POAG但未携带Gln368STOP突变的个体。对于这些个体，诊断时的平均年龄更高（62.3±13.7岁，P<0.01），平均眼压峰值更低（25.4±6.4 mmHg，P = 0.01）。对于Gln368STOP突变携带者，40岁时OHT或POAG的年龄相关外显率为72%，65岁时为82%。所有索引病例均有POAG的阳性家族史。8个家系中有5个家系在母系和父系均有阳性家族史。8个家系中有7个家系有一名或多名患有POAG但未携带该突变的个体。29名患有OHT或POAG的Gln368STOP突变携带者中有8人接受了小梁切除术。
GLC1A Gln368STOP突变与POAG相关，在所研究的家系中，与非突变型青光眼病例相比，其发病年龄更小，眼压峰值更高。此外，Gln368STOP突变型青光眼病例更有可能接受青光眼引流手术。在这些家系中，我们未观察到POAG的简单常染色体显性遗传模式。其他尚未明确的因素参与了Gln368STOP家系中POAG表型的表达。
