IRO - Institute for Research in Ophthalmology, Sion, Switzerland.
Genetics Unit, Department of Pediatrics, University of Alexandria, Alexandria, Egypt.
Adv Exp Med Biol. 2019;1185:221-226. doi: 10.1007/978-3-030-27378-1_36.
Anophthalmia and microphthalmia (A/M) are rare distinct phenotypes that represent a continuum of structural developmental eye defects. Here, we describe three probands from an Egyptian population with various forms of A/M: two patients with bilateral anophthalmia and one with bilateral microphthalmia that were investigated using whole exome sequencing (WES). We identified three causative mutations in three different genes. A new homozygous frameshift mutation c.[422delA];[422delA], p.[N141Ifs∗19];[N141Ifs∗19] in VSX2 was identified in a patient showing bilateral anophthalmia. A previously reported SOX2 deletion c.[70_89del20] p.[N24Rfs∗65];[=] was found in one subject with bilateral anophthalmia. A novel homozygous in-frame mutation c.[431_433delACT];[431_433delACT], p.[Y144del]; [Y144del]) in FOXE3 was identified in a patient with severe bilateral microphthalmia and anterior segment dysgenesis. This study shows that whole exome sequencing (WES) is a reliable and effective strategy for the molecular diagnosis of A/M. Our results expand its allelic heterogeneity and highlight the need for the testing of patient with this developmental anomaly.
先天性无眼症和小眼球症(A/M)是罕见的独特表型,代表了结构发育性眼部缺陷的连续谱。在这里,我们描述了来自埃及人群的三个具有各种形式 A/M 的先证者:两名双侧无眼症患者和一名双侧小眼球症患者,他们接受了全外显子组测序(WES)的检查。我们在三个不同的基因中发现了三个致病突变。在表现为双侧无眼症的患者中发现了一个新的纯合移码突变 c.[422delA];[422delA],p.[N141Ifs∗19];[N141Ifs∗19] 在 VSX2 中。一个以前报道的 SOX2 缺失 c.[70_89del20] p.[N24Rfs∗65];[=] 在另一名双侧无眼症患者中发现。在一名严重双侧小眼球症和前节发育不良的患者中发现了 FOXE3 中的一个新的纯合框内突变 c.[431_433delACT];[431_433delACT],p.[Y144del];[Y144del])。这项研究表明,全外显子组测序(WES)是 A/M 分子诊断的可靠有效的策略。我们的结果扩展了其等位基因异质性,并强调了对具有这种发育异常的患者进行检测的必要性。