Penetrance and Phenotype of the Thr377Met Myocilin Mutation in a Large Finnish Family with Juvenile- and Adult-Onset Primary Open-Angle Glaucoma
Penetrance and Phenotype of the Thr377Met Myocilin Mutation in a Large Finnish Family with Juvenile- and Adult-Onset Primary Open-Angle Glaucoma
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DOI：
10.1080/13816810590918208
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发表时间：
2005-01
影响因子：
1.2
通讯作者：
P. Puska;S. Lemmelä;P. Kristo;E. Sankila;I. Järvelä
中科院分区：
文献类型：
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作者：
P. Puska;S. Lemmelä;P. Kristo;E. Sankila;I. Järvelä
目的：目的研究肌球蛋白（myocilin，MYOC）作为青少年型和成人型开角型青光眼（JOAG和POAG）易感基因的作用。研究方法：在一个六代的芬兰家族中，我们对51名患有JOAG和POAG的患者进行了彻底的眼科表征（包括通过Octopus视野检查评估视野，通过摄影评估神经纤维层厚度，通过海德堡断层扫描评估椎间盘大小）。通过PCR扩增和直接测序筛选MYOC编码区的突变。结果：我们检测到密码子377处的C > T转换，导致Myocilin的嗅觉调节素样结构域中的苏氨酸残基取代甲硫氨酸（Thr 377 Met），在家族中分离。在20例突变杂合子中，9例（45%）为青光眼，2例（10%）为高眼压（OHT）。这些个体诊断青光眼的平均年龄为34.3岁（范围：14-66岁）。此外，其中三个人的一只眼睛患有视网膜静脉阻塞（RVO），而一个没有突变的人患有RVO。结论：MYOC中Thr 377 Met突变可能是青光眼的易感等位基因。这些发现可能有助于遗传咨询，早期诊断和治疗青光眼。与Thr 377 Met突变一起导致RVO的因素的可能相互作用值得进一步研究。
Purpose: To study the role of myocilin (MYOC) as a susceptibility gene for juvenile- and adult-onset open-angle glaucoma (JOAG and POAG, respectively). Methods: In a six-generation Finnish family with JOAG and POAG, we performed thorough ophthalmologic characterization (including assessment of the visual fields by Octopus perimetry, nerve-fiber layer thickness by photography, and disc size by Heidelberg tomography) of 51 individuals. The coding region of MYOC was screened for mutations by PCR amplification and direct sequencing. Results:We detected a C > T transition at codon 377 resulting in a substitution of a threonine residue for methionine (Thr377Met) in the olfactomedin-like domain of myocilin, segregating in the family. Of the 20 individuals heterozygous for the mutation, nine (45%) were glaucomatous and two (10%) had ocular hypertension (OHT). The mean age at diagnosis of glaucoma in these individuals was 34.3 years (range: 14-66 years). Moreover, three of these individuals suffered retinal vein occlusion (RVO) in one eye, while one individual without the mutation had RVO. Conclusion:Our results further support the evidence that the Thr377Met mutation in MYOC may represent a susceptibility allele for glaucoma. These findings may facilitate genetic counseling, and early diagnosis and treatment of glaucoma. The possible interaction of factors contributing to RVO in conjunction with the Thr377Met mutation warrants further investigation.