State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Invest Ophthalmol Vis Sci. 2012 Sep 19;53(10):6338-42. doi: 10.1167/iovs.12-10472.
Mutations in paired box gene 6 (PAX6) are the major cause of aniridia that may associate with several other developmental anomalies of the eye, including microcornea in rare cases. However, systemic evaluation of PAX6 in patients with microcornea as the major sign has not been reported. This study aims to detect PAX6 mutations in patients with microcornea.
Genomic DNA of probands was prepared from 35 families with microcornea. The coding regions of PAX6 were screened by Sanger sequencing and novel variations were further evaluated in 192 normal individuals. Bioinformatics analysis was used to evaluate the structural consequences related to the pathology of the mutations.
The average corneal horizontal diameter of the 35 probands is 8.03 ± 1.27 mm (the median value is 8 mm). Among them, eight patients presented with normal iris, one had aniridia, and different severities of iris hypoplasia were detected in the rest. In four probands, three heterozygous variations in PAX6 were identified: a novel c.83_85delAGA (p.Lys28del) in two families; a novel c.337G>C (p.Ala113Pro) in one family; and a known c.399_399+5del6 in one family. None of the variations were detected in 192 normal individuals. Two of the four probands had partial iris while the other two presented with full iris.
We identified two novel and a known mutation of PAX6 in four probands with microcornea, accounting for 11.4% of microcorneas in this cohort. The findings not only expand the spectrum of PAX6 mutations, but also suggest that PAX6 mutations may be a common cause of microcornea.
配对盒基因 6（PAX6）突变是无虹膜的主要原因，无虹膜可能与眼睛的其他几种发育异常有关，包括在极少数情况下的小角膜。然而，以小角膜为主要特征的患者中 PAX6 的系统评估尚未有报道。本研究旨在检测小角膜患者的 PAX6 突变。
从小角膜的 35 个家系中提取先证者的基因组 DNA。通过 Sanger 测序筛选 PAX6 的编码区，对 192 名正常个体中的新变异进行进一步评估。使用生物信息学分析评估与突变相关的病理结构后果。
35 名先证者的角膜水平直径平均为 8.03±1.27mm（中位数为 8mm）。其中 8 例患者的虹膜正常，1 例患者为无虹膜，其余患者的虹膜发育不全程度不同。在 4 名先证者中，发现了 PAX6 的三个杂合变异：两个家系中出现了一个新的 c.83_85delAGA（p.Lys28del）；一个家系中出现了一个新的 c.337G>C（p.Ala113Pro）；一个家系中出现了一个已知的 c.399_399+5del6。这 4 种变异在 192 名正常个体中均未检测到。这 4 名先证者中有 2 名部分虹膜，另外 2 名完全虹膜。
我们在 4 名小角膜先证者中发现了 PAX6 的两个新突变和一个已知突变，占该队列中小角膜的 11.4%。这些发现不仅扩大了 PAX6 突变谱，而且提示 PAX6 突变可能是小角膜的一个常见原因。
