Wawrocka Anna, Budny Bartlomiej, Debicki Szymon, Jamsheer Aleksander, Sowinska Anna, Krawczynski Maciej Robert
Department of Medical Genetics, Poznan University of Medical Science, Poznan, Poland.
Ophthalmic Genet. 2012 Mar;33(1):44-8. doi: 10.3109/13816810.2011.615076. Epub 2011 Oct 10.
Aniridia is a congenital panocular malformation defined as iris aplasia or hypoplasia. It can be either isolated or be a part of multiple ocular anomalies such as cataracts, glaucoma, corneal pannus, optic nerve hypoplasia, absence of macular reflex or ectopia lentis. In the majority of cases the disease is caused by mutation in the PAX6 gene.
A Polish family with aniridia was screened for the presence of genomic rearrangements in PAX6, WT1 and the flanking genes by means of multiplex ligation probe amplification (MLPA). MLPA reaction was performed using the P219-B1 PAX6 commercial kit from MRC-Holland. Additionally, the coding sequence of PAX6 gene was sequenced in the proband. Array comparative genomic hybridization analysis was performed using the NimbleGen CGX-12 format.
MLPA examination revealed a heterozygous deletion of approximately 0.6 Mb, downstream of PAX6 gene on chromosome 11. Four genes lie in the deleted region. Bi-directional sequencing of 14 exons of the PAX6 gene did not reveal any causative alteration. Microarray analysis confirmed the deletion and determined its size which ranged from 598.87-651.76 kb.
A small subset of aniridia cases is caused by rearrangements of PAX6 neighboring regions, and the so-called "position effect" is considered to be the underlying pathogenic mechanism. Molecular testing of aniridia patients should include sequencing of the PAX6 gene, followed by screening for larger structural abnormalities located on chromosome 11p13. MLPA can be a useful method in molecular testing of aniridia patients.
无虹膜症是一种先天性全眼畸形，定义为虹膜发育不全或发育不良。它可以是孤立的，也可以是多种眼部异常的一部分，如白内障、青光眼、角膜血管翳、视神经发育不全、黄斑反射缺失或晶状体异位。在大多数情况下，该疾病是由PAX6基因突变引起的。
通过多重连接探针扩增（MLPA）对一个患有无虹膜症的波兰家族进行PAX6、WT1及侧翼基因的基因组重排检测。使用MRC-荷兰公司的P219-B1 PAX6商业试剂盒进行MLPA反应。此外，对先证者的PAX6基因编码序列进行测序。使用NimbleGen CGX-12格式进行阵列比较基因组杂交分析。
MLPA检测显示11号染色体上PAX6基因下游存在约0.6 Mb的杂合缺失。四个基因位于缺失区域。对PAX6基因的14个外显子进行双向测序未发现任何致病改变。微阵列分析证实了该缺失并确定其大小范围为598.87 - 651.76 kb。
一小部分无虹膜症病例是由PAX6邻近区域的重排引起的，所谓的“位置效应”被认为是潜在的致病机制。无虹膜症患者的分子检测应包括PAX6基因测序，随后筛查位于11号染色体p13上的更大结构异常。MLPA可作为无虹膜症患者分子检测的一种有用方法。
