Childhood glaucoma genes and phenotypes: Focus on FOXC1 mutations causing anterior segment dysgenesis and hearing loss
Childhood glaucoma genes and phenotypes: Focus on FOXC1 mutations causing anterior segment dysgenesis and hearing loss
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DOI：
10.1016/j.exer.2019.107893
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发表时间：
2020-01-01
影响因子：
3.4
通讯作者：
Wiggs, Janey L.
中科院分区：
文献类型：
--
作者：
Gauthier, Angela C.;Wiggs, Janey L.
儿童青光眼是全世界失明的重要原因。目前已知有 11 个基因会导致 20 岁之前发病的遗传性青光眼。虽然所有早发性青光眼基因都会导致严重的疾病，但在突变携带者中观察到相当大的表型变异。特别是，FOXC1 基因变异与多种表型相关，包括多种形式的青光眼以及全身异常，尤其是听力损失。 FOXC1 是转录因子叉头家族的成员，参与形成前眼结构以及形成中耳骨的咽弓所必需的神经嵴发育。在这项研究中，我们回顾了已知 FOXC1 突变的临床表型，并表明眼前段异常和听力损失患者的突变主要破坏了至关重要的叉头结构域。这些结果表明，对眼前节发育不全患者的最佳护理应包括筛查 FOXC1 突变和检测听力损失。
Childhood glaucoma is an important cause of blindness world-wide. Eleven genes are currently known to cause inherited forms of glaucoma with onset before age 20. While all the early-onset glaucoma genes cause severe disease, considerable phenotypic variability is observed among mutations carriers. In particular, FOXC1 genetic variants are associated with a broad range of phenotypes including multiple forms of glaucoma and also systemic abnormalities, especially hearing loss. FOXC1 is a member of the forkhead family of transcription factors and is involved in neural crest development necessary for formation of anterior eye structures and also pharyngeal arches that form the middle ear bones. In this study we review the clinical phenotypes reported for known FOXC1 mutations and show that mutations in patients with reported ocular anterior segment abnormalities and hearing loss primarily disrupt the critically important forkhead domain. These results suggest that optimal care for patients affected with anterior segment dysgenesis should include screening for FOXC1 mutations and also testing for hearing loss.