Polymerase chain reaction-based risk assessment for Wilms tumor in sporadic aniridia.
OBJECTIVE
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.
Gupta
S K
SK
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
De Becker
I
I
Guernsey
D L
DL
Neumann
P E
PE
D015783:Aniridia / Q000150:complications / Q000235:genetics*; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004247:DNA / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D016162:Genes, Wilms Tumor / Q000235:genetics; D005838:Genotype; D018398:Homeodomain Proteins; D006801:Humans; D007680:Kidney Neoplasms / Q000150:complications / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D016133:Polymerase Chain Reaction / Q000379:methods; D012097:Repressor Proteins; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000235:genetics*; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000150:complications / Q000235:genetics*
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D004247:DNA