Homozygous Mutations in PXDN Cause Congenital Cataract, Corneal Opacity, and Developmental Glaucoma
Homozygous Mutations in PXDN Cause Congenital Cataract, Corneal Opacity, and Developmental Glaucoma
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DOI：
10.1016/j.ajhg.2011.08.005
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发表时间：
2011-09-09
影响因子：
9.8
通讯作者：
Ali, Manir
中科院分区：
文献类型：
--
作者：
Khan, Kamron;Rudkin, Adam;Ali, Manir
前段发育不良描述了一组影响眼睛前房的异质发育障碍，并与青光眼的风险增加有关。在这里，我们报告了两个近亲巴基斯坦家族先天性白内障小角膜伴轻度至中度角膜混浊和一个近亲柬埔寨家族伴发育性青光眼伴严重角膜平化的过氧化物酶（PXDN）纯合突变。这些结果强调了PXDN突变引起的多种眼部表型，这可能是由于遗传背景和环境因素的差异。过氧化物酶是一种细胞外基质相关蛋白，具有过氧化物酶催化活性，我们证实该蛋白定位于角膜和晶状体上皮层。我们的研究结果表明，过氧化物酶对眼睛前房的正常发育至关重要，它可能具有支持角膜和晶状体结构的结构作用，以及作为抗氧化酶保护晶状体、小梁网和角膜免受氧化损伤的酶作用。
Anterior segment dysgenesis describes a group of heterogeneous developmental disorders that affect the anterior chamber of the eye and are associated with an increased risk of glaucoma. Here, we report homozygous mutations in peroxidasin (PXDN) in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal pacification. These results highlight the diverse ocular phenotypes caused by PXDN mutations, which are likely due to differences in genetic background and environmental factors. Peroxidasin is an extracellular matrix-associated protein with peroxidase catalytic activity, and we confirmed localization of the protein to the cornea and lens epithelial layers. Our findings imply that peroxidasin is essential for normal development of the anterior chamber of the eye, where it may have a structural role in supporting cornea and lens architecture as well as an enzymatic role as an antioxidant enzyme in protecting the lens, trabecular meshwork, and cornea against oxidative damage.