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Polymerase chain reaction-based risk assessment for Wilms tumor in sporadic aniridia
S K Gupta1, I De Becker, D L Guernsey
1Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Insights
A new DNA test can rule out chromosome 11p13 deletions in sporadic aniridia (a rare eye condition). This test helps identify patients who do not need regular ultrasounds for Wilms tumor screening.
Area of Science:
- Genetics and Molecular Biology
- Ophthalmology
- Pediatric Oncology
Background:
- Sporadic aniridia presents a 30% risk of Wilms tumor development.
- Current screening involves biannual renal ultrasonography until age 5.
- The PAX6 and WT1 gene loci deletion on chromosome 11p13 underlies this association.
Purpose of the Study:
- To develop a rapid polymerase chain reaction (PCR)-based test.
- To effectively rule out chromosome 11p13 deletions in sporadic aniridia patients.
Main Methods:
- Recruited five patients with sporadic aniridia.
- Conducted PCR-based genotyping across the PAX6-WT1 region.
- Compared results with cell lines having known deletions.
Main Results:
- All patients were heterozygous, indicating no gross deletions.
- Cell lines showed hemizygosity within the critical region.
Conclusions:
- Developed a rapid DNA test with 94.0%-99.2% sensitivity.
- This test rules out chromosomal deletion in sporadic aniridia.
- Negative results obviate the need for routine renal imaging for Wilms tumor.
Purpose:
Sporadic cases of aniridia have a 30% risk for the development of Wilms tumor. Current guidelines for sporadic aniridia recommend screening by renal ultrasonography for the presence of tumors every 6 months until age 5 years. Deletions of chromosome 11p13 that affect both PAX6 (aniridia) and WT1 (Wilms tumor) loci are the basis for the association of these two uncommon disorders. We sought to develop a rapid polymerase chain reaction-based test that could rule out a chromosome 11p13 deletion covering the PAX6-WT1 region in sporadic aniridia.
Methods:
Five patients with sporadic aniridia were recruited. Polymerase chain reaction-based genotyping was carried out for six highly informative marker loci across the PAX6-WT1 region to determine whether these patients had one or two haplotypes. The results were compared with those obtained from two cell lines with known deletions in the PAX6-WT1 region.
Results:
All five patients were heterozygous at least at one of the four marker loci in the PAX6-WT1 region, indicating that there were no cases of gross chromosomal deletion. The cell lines showed hemizygosity in the four marker loci within the PAX6-WT1 region and in one of the two flanking marker loci.
Conclusions:
We have developed a rapid DNA test with an estimated sensitivity of 94.0% to 99.2%, using standard DNA diagnostic techniques and equipment, to rule out chromosomal deletion in sporadic aniridia. Patients in whom a chromosome 11p13 deletion has been ruled out do not require repeated renal imaging to screen for Wilms tumor.