Osteogenesis imperfecta and primary open angle glaucoma: Genotypic analysis of a new phenotypic association
Osteogenesis imperfecta and primary open angle glaucoma: Genotypic analysis of a new phenotypic association
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发表时间：
2014-08
期刊：
影响因子：
2.2
通讯作者：
Dana J. Wallace;Felix Chau;C. Santiago-Turla;M. Hauser;P. Challa;Paul P. Lee;L. Herndon;R. Allingham;R. Allingham
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文献类型：
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作者：
Dana J. Wallace;Felix Chau;C. Santiago-Turla;M. Hauser;P. Challa;Paul P. Lee;L. Herndon;R. Allingham;R. Allingham
目的成骨不全是一组以骨脆性为特征的遗传性疾病。眼部表现包括巩膜发青、眼球僵硬程度降低和角膜厚度变薄。然而，目前尚无OI与原发性开角型青光眼(POAG)相关的文献记载。在这份报告中，我们描述了三个人，一个孤立病例和两个来自多个家庭，患有OI I型和POAG。方法对OI和POAG的家系成员进行全面的眼科检查，包括视力、眼压、角膜厚度、裂隙灯检查、扩张眼底检查和视野检查。对血液样本中的DNA进行测序，并筛选COL1A1/2和myoclin(MYOC)突变。结果所有受试者均为OI I型，POAG的表现包括眼压升高、房角镜检查正常、青光眼视盘拔罐和视野丧失。POAG与Oi在多种多样的家族中共分离。该多重家族在COL1A1中有一个单核苷酸插入(c.540_541insC)，导致一个移码突变和一个提前终止密码子。这例散发性病例存在COL1A1剪接受体位点突变(C.2452-2A>；T或IVS36-2A>；T)，预计会由于内含子包含或隐蔽的剪接位点而导致提前终止密码子。所有青光眼患者均未发现MYOC基因突变或序列改变。结论我们在OI I型和POAG患者中发现了两个新的COL1A1突变。因此，COL1A1的某些突变可能是OI和POAG的致病因素。或者，易感基因可能与COL1A1突变相互作用而导致POAG。
Purpose Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility. Ocular findings include blue sclera, low ocular rigidity, and thin corneal thickness. However, there are no documented cases linking OI and primary open angle glaucoma (POAG). In this report, we describe three individuals, one isolated case and two from a multiplex family, with OI type I and POAG. Methods Available family members with OI and POAG had a complete eye examination, including visual acuity, intraocular pressure (IOP), pachymetry, slit-lamp exam, dilated fundus exam, and visual fields. DNA from blood samples was sequenced and screened for mutations in COL1A1/2 and myocilin (MYOC). Results All subjects had OI type I. Findings of POAG included elevated IOP, normal gonioscopy, and glaucomatous optic disc cupping and visual field loss. POAG cosegregated with OI in the multiplex family. The multiplex family had a single nucleotide insertion (c.540_541insC) in COL1A1 resulting in a frameshift mutation and a premature termination codon. The sporadic case had a COL1A1 splice acceptor site mutation (c.2452–2A>T or IVS36–2A>T) predicted to result in a premature termination codon due to intron inclusion or a cryptic splice site. None of the glaucoma cases had mutations or sequence changes in MYOC. Conclusions We identified two novel mutations in COL1A1 in individuals with OI type I and POAG. Thus, some mutations in COL1A1 may be causative for OI and POAG. Alternatively, susceptibility genes may interact with mutations in COL1A1 to cause POAG.