WAGR syndrome is a rare genetic disorder associated with the deletion of chromosome 11p13, involving genes WT1 and PAX6, and features Wilms’ tumor, aniridia, genitourinary anomalies, as well as varying degrees of intellectual disabilities. Some other findings may include obesity, glaucoma, cataracts, kidney failure, congenital diaphragmatic hernia, and autism. Wang et al. presents 6 Chinese WAGR patients to expand our knowledge of the genotype-phenotype relationship in WAGR syndrome. The 6 patients had de novo deletions located at 11p13 varying from as small as 1.99Mb in Patient 6 to as large as 16.46Mb in Patient 1. All patients showed aniridia and cataracts. Aniridia and associated ocular defects are attributed to a PAX6 haploinsufficiency that is required for eye development. A regulatory element of PAX6 is SIMO, located next to the gene; mis-regulation of the SIMO element contributes to the defective expression of PAX6, suggesting that a co-deletion of PAX6 and SIMO could lead to a more severe ocular phenotype. In the presented case, all patients had the SIMO element affected except for Patient 6, who had the mildest ocular phenotype observed. 3 out of 6 patients had glaucoma before or after cataract surgery. 3/6 patients presented with thin lens and keratolenticular adhesion with corneal neovascularization; the cloudy lens of Patient 1 was partially absorbed during a follow-up when they were 2 years old. The ARL13EP gene was deleted in all four probands with severe lens abnormalities and was unaffected in two patients without severe lens abnormalities. The authors suggest that damage of ARL13EP could lead to increased risk for severe lens abnormalities in 11p13 deletion patients. Although not statistically significant these data suggests that further studies must be done to investigate the genotype-phenotype correlation of 11p13 deletions. 4 out of 6 patients developed Wilms tumor before the age of 2. Some authors suggest that deletion of the neighboring LOMO2 gene may increase probability of Wilms’ tumor. All 4 probands that developed Wilms’ tumor before 2 years old had a LMO2 deletion and a patient without a LMO2 deletion was tumor-free at the age of 11. However, one patient with a LMO2 deletion had no signs of Wilms’ tumor at the age of 3.
Wang et al. “Unusual Presentation in WAGR Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Diseases”. “Genes”(Basel) 2022, v.13:1431. WAGR syndrome 11p13 deletion
Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact email@example.com