Abstract for presentation at 11th International Congress of Human Genetics

Aniridia and the 11p13 region: G-banding difficulties and the requirement for FISH/CGH Array to define PAX6 and WT1 status

  • Mr Luke St Heaps, Department of Cytogenetics, The Children's Hospital at Westmead, Sydney, New South Wales., Australia
  • Dr John Grigg, Save Sight Insitute, University of Sydney, Australia
  • Mrs Nicole Chia, Cytogenetics, ACT Pathology , Canberra Hospital, Australia
  • Dr Greg Peters, 3Cytogenetics Department, Western Sydney Genetics Program, Children’s Hospital at Westmead NSW, Australia
  • Dr Robyn Jamieson, Eye Genetics Group Children’s Medical Research Institute, Discipline of Paediatrics & Child Health, University of Sydney, Australia

    • Aniridia is a congenital malformation of the anterior segment of the eye characterised by near or complete absence of the iris. It is a panocular disorder affecting the cornea, lens, fovea and the optic nerve. Haploinsufficiency of the PAX6 gene on chromosome 11p13 is known to cause aniridia. Approximately 40% of the sporadic cases and 10% of the familial cases occur as a result of cytogenetically visible or cryptic deletions. When deletion extends to include the adjacent WT1 gene, patients are predisposed to developing Wilms tumour with an increased risk of up to 60%. We are testing a cohort of patients with aniridia and related ocular anterior segment anomalies with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) micro-array analysis in search of deletion/rearrangement within 11p13. A series of eight bacterial clones containing cosmids spanning and flanking the WT1/PAX6 region are being used in FISH. We are developing a further 47 clones spanning chromosome 11p for CGH array to provide a more rapid and expansive protocol. In 13 aniridia referral patients tested so far, 4 have been found to have deletions and in 3 these were defined only after FISH analysis. Although a deletion was detected on a routine karyotype in one of these patients, the breakpoints suggested placed the patient at risk of Wilms tumour development due to inferred loss of WT1. However, FISH with the WT1 probe showed this locus was intact. This result created a real conundrum and necessitated revision of both the cytogenetic breakpoints and the patient's Wilms tumour risk. This highlights the need for FISH/CGH array investigation, as patients with aniridia are at high risk of Wilms tumour if WT1 is deleted and some patients with a cytogenetically visible deletion may be placed in a high risk category for Wilms even though WT1 is not deleted. We aim to now expand our investigation of this region using a CGH array to more clearly define the extent of these deletions.

    Conference Organiser - ICMS Pty Ltd