Poznan University of Medical Sciences, 60-352, Poznan, Poland.
J Appl Genet. 2013 Aug;54(3):345-51. doi: 10.1007/s13353-013-0154-0. Epub 2013 Jun 13.
Aniridia is a rare, bilateral, congenital ocular disorder causing incomplete formation of the iris, usually characterized by iris aplasia/hypoplasia. It can also appear with other ocular anomalies, such as cataracts, glaucoma, corneal pannus, optic nerve hypoplasia, macular hypoplasia, or ectopia lentis. In the majority of cases, it is caused by mutation in the PAX6 gene, but it can also be caused by microdeletions that involve the 11p13 region. Twelve unrelated patients of Polish origin with a clinical diagnosis of aniridia were screened for the presence of microdeletions in the 11p13 region by means of multiplex ligation probe amplification (MLPA). Additionally, the coding regions of the PAX6 gene were sequenced in all probands. MLPA examination revealed different size deletions of the 11p13 region in five patients. In three cases, deletions encompassed the entire PAX6 gene and a few adjacent genes. In one case, a fragment of the PAX6 gene was deleted only. In the final case, the deletion did not include any PAX6 sequence. Our molecular findings provide further evidence of the existence of the distant 3' regulatory elements in the downstream region of the PAX6 gene, which is known from other studies to influence the level of protein expression. Sequence analysis of the PAX6 gene revealed the three different point mutations in the remaining four patients with aniridia. All the detected mutations were reported earlier. Based on accomplished results, the great diversity of the molecular basis of aniridia was found. It varies from point mutations to different size deletions in the 11p13 region which encompass partly or completely the PAX6 gene or cause a position effect.
先天性虹膜缺损是一种罕见的双侧先天性眼部疾病,导致虹膜不完全形成,通常表现为虹膜发育不全/发育不良。它也可能与其他眼部异常一起出现,如白内障、青光眼、角膜血管翳、视神经发育不良、黄斑发育不良或晶状体异位。在大多数情况下,它是由 PAX6 基因突变引起的,但也可能是由涉及 11p13 区域的微缺失引起的。对 12 名来自波兰的、具有先天性虹膜缺损临床诊断的无关患者进行了 11p13 区域微缺失的多重连接探针扩增 (MLPA) 筛查。此外,对所有先证者进行了 PAX6 基因编码区的测序。MLPA 检查显示,在 5 名患者中存在 11p13 区域的不同大小缺失。在 3 例中,缺失涵盖了整个 PAX6 基因和几个相邻基因。在 1 例中,仅缺失了 PAX6 基因的一个片段。在最后 1 例中,缺失不包括任何 PAX6 序列。我们的分子研究结果进一步证明了 PAX6 基因下游区域存在远距离 3' 调控元件,这在其他研究中已知会影响蛋白质表达水平。对 PAX6 基因的序列分析显示,在另外 4 名具有先天性虹膜缺损的患者中发现了 3 个不同的点突变。所有检测到的突变都有报道过。基于已完成的结果,发现先天性虹膜缺损的分子基础具有很大的多样性。它从点突变到 11p13 区域的不同大小缺失不等,这些缺失部分或完全包含 PAX6 基因,或引起位置效应。