Grant Madison K, Bobilev Anastasia M, Pierce Jordan E, DeWitte Jon, Lauderdale James D
Department of Cellular Biology, University of Georgia, Athens, GA, 30602, USA.
Neuroscience Division of the Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, 30602, USA.
F1000Res. 2017 Mar 13;6:255. doi: 10.12688/f1000research.11063.2. eCollection 2017.
Aniridia is a disorder predominately caused by heterozygous loss-of-function mutations of the gene, which is a transcriptional regulator necessary for normal eye and brain development. The ocular abnormalities of aniridia have been well characterized, but mounting evidence has implicated brain-related phenotypes as a prominent feature of this disorder as well. Investigations using neuroimaging in aniridia patients have shown reductions in discrete brain structures and changes in global grey and white matter. However, limited sample sizes and substantive heterogeneity of structural phenotypes in the brain remain a challenge. Here, we examined brain structure in a new population sample in an effort to add to the collective understanding of anatomical abnormalities in aniridia. The current study used 3T magnetic resonance imaging to acquire high-resolution structural data in 12 persons with aniridia and 12 healthy demographically matched comparison subjects. We examined five major structures: the anterior commissure, the posterior commissure, the pineal gland, the corpus callosum, and the optic chiasm. The most consistent reductions were found in the anterior commissure and the pineal gland; however, abnormalities in all of the other structures examined were present in at least one individual. Our results indicate that the anatomical abnormalities in aniridia are variable and largely individual-specific. These findings suggest that future studies investigate this heterogeneity further, and that normal population variation should be considered when evaluating structural abnormalities.
无虹膜症是一种主要由该基因的杂合功能丧失突变引起的疾病，该基因是正常眼睛和大脑发育所必需的转录调节因子。无虹膜症的眼部异常已得到充分表征，但越来越多的证据表明，与大脑相关的表型也是这种疾病的一个突出特征。对无虹膜症患者进行的神经影像学研究表明，离散脑结构体积减小，全脑灰质和白质发生变化。然而，样本量有限以及大脑结构表型存在实质性异质性仍然是一个挑战。在此，我们对一个新的人群样本进行了脑结构检查，以期增进对无虹膜症解剖学异常的总体认识。当前研究使用3T磁共振成像技术，获取了12名无虹膜症患者和12名年龄、人口统计学特征匹配的健康对照者的高分辨率结构数据。我们检查了五个主要结构：前连合、后连合、松果体、胼胝体和视交叉。在前连合和松果体中发现了最一致的体积减小；然而，在所检查的所有其他结构中，至少有一名个体存在异常。我们的结果表明，无虹膜症的解剖学异常是可变的，且在很大程度上是个体特异性的。这些发现表明，未来的研究应进一步探究这种异质性，并且在评估结构异常时应考虑正常人群的变异情况。
