Allingham R R, Wiggs J L, De La Paz M A, Vollrath D, Tallett D A, Broomer B, Jones K H, Del Bono E A, Kern J, Patterson K, Haines J L, Pericak-Vance M A
Duke University Medical Center, Durham, North Carolina, USA.
Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2288-95.
To examine families ascertained for late-onset primary open-angle glaucoma (POAG) to determine mutations in the gene coding for myocilin.
The diagnosis of late-onset POAG was defined as age at diagnosis more than 35 years, intraocular pressure (IOP) 22 mm Hg or more in both eyes or 19 mm Hg or more while the patient was taking two glaucoma medications, glaucomatous optic neuropathy in both eyes, and visual field loss consistent with optic nerve damage in at least one eye of the proband. Two of three criteria were required in other family members. DNA from all families was screened for polymorphisms in myocilin using single-strand conformation polymorphism analysis. All polymorphisms were sequenced for mutations.
Eighty-three affected people in 29 families with late-onset POAG were screened for mutations. Three mutations, two novel missense (Thr377Met and Glu352Lys) and one nonsense (Gln368STOP), were identified. The missense mutations did not segregate with the disease phenotype in these families. The nonsense mutation was found in 3 of 29 unrelated families with POAG. All affected family members and 8 of 12 in whom glaucoma was suspected had the Gln368STOP mutation. All people with this mutation had elevated IOP, and 78% had POAG by age 70.
Three mutations were identified in the gene coding for myocilin in families with late-onset POAG. Of these, the Gln368STOP mutation was highly associated with the development of glaucoma. All people with this mutation had glaucoma or elevated IOP by age 70. In the United States, the Gln368STOP mutation in myocilin is strongly associated with the development of late-onset POAG. However, factors in addition to the presence of this mutation seem to play a role in the development of ocular hypertension and glaucoma in these families.
对因迟发性原发性开角型青光眼（POAG）确诊的家族进行研究，以确定编码肌纤蛋白的基因突变情况。
迟发性POAG的诊断标准为：确诊年龄超过35岁，双眼眼压（IOP）≥22 mmHg，或患者正在使用两种青光眼药物时眼压≥19 mmHg，双眼存在青光眼性视神经病变，且先证者至少一只眼存在与视神经损伤相符的视野缺损；其他家庭成员需满足三项标准中的两项。使用单链构象多态性分析对所有家族的DNA进行肌纤蛋白多态性筛查。对所有多态性进行测序以检测突变。
对29个迟发性POAG家族中的83名患者进行了突变筛查。共鉴定出三个突变，两个为新的错义突变（Thr377Met和Glu352Lys），一个为无义突变（Gln368STOP）。这些家族中的错义突变与疾病表型不连锁。在29个无关的POAG家族中有3个发现了无义突变；所有受影响的家族成员以及12名疑似青光眼患者中的8名携带Gln368STOP突变。所有携带该突变的人眼压均升高，78%在70岁时患有POAG。
在迟发性POAG家族中，编码肌纤蛋白的基因鉴定出三个突变。其中，Gln368STOP突变与青光眼的发生高度相关。所有携带该突变的人在70岁时均患有青光眼或眼压升高。在美国，肌纤蛋白中的Gln368STOP突变与迟发性POAG的发生密切相关。然而，除该突变外的其他因素似乎在这些家族的高眼压症和青光眼的发生中也起作用。
