BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. MATERIAL AND METHODS: 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. RESULTS: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. CONCLUSIONS: 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 aniridiapatients 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 aniridiapatients.
Authors: Sarah F Janssen; Theo G M F Gorgels; Koen Bossers; Jacoline B Ten Brink; Anke H W Essing; Martijn Nagtegaal; Peter J van der Spek; Nomdo M Jansonius; Arthur A B Bergen Journal: PLoS One Date: 2012-09-18 Impact factor: 3.240
Authors: Fiona Blanco-Kelly; María Palomares; Elena Vallespín; Cristina Villaverde; Rubén Martín-Arenas; Camilo Vélez-Monsalve; Isabel Lorda-Sánchez; Julián Nevado; María José Trujillo-Tiebas; Pablo Lapunzina; Carmen Ayuso; Marta Corton Journal: PLoS One Date: 2017-02-23 Impact factor: 3.240
Authors: Grace M Wang; Lev Prasov; Hayder Al-Hasani; Colin E R Marrs; Sahil Tolia; Laurel Wiinikka-Buesser; Julia E Richards; Brenda L Bohnsack Journal: J Ophthalmol Date: 2018-04-04 Impact factor: 1.909