Wagr Syndrome

WAGR Syndrome WAGR (Wilms’ tumor, Aniridia, Genitourinary abnormalities, and mental Retardation) Syndrome is a contiguous gene deletion syndrome that is caused by a deletion in chromosome 11. The acronym for the syndrome comes from the various symptoms that are caused by the deletion – wilms’ tumor, aniridia, genitourinary abnormalities, and mental retardation. Wilms’ tumor is a tumor that is found in the kidneys that causes nephroblastoma, cancer of the kidneys. Aniridia, the absence of the iris, is found in the majority of cases, and is required, along with one of the other three symptoms, to diagnose the syndrome. Genitourinary abnormalities are often seen, and easily detected since genital abnormalities are physically evident. Finally, nearly every WAGR patient is at least mildly mentally retarded. Some of these traits have been explained by genes on chromosome 11, but others, like mental retardation, are yet to be fully explained. Extensive research of the short arm of chromosome 11, where the deletion occurs, has and still is being done to discover the answers of this syndrome, along with the answers to other cancers (lung and heart) that it seems to cause. (Almind, et al., 2009; Tyagi, et al., 2008) Sequence analysis of chromosomal region 11p13-14 shows that there are 7 genes contained within the region – WT1, BDNF, KCNA4, FSHB, 239FB, PAX6, and RCN1. Four of these genes (WT1, BDNF, 239FB, PAX6) have some type of relation with WAGR syndrome. In a case study reported by Almind et al, a child with bilateral ptosis (drooping of the upper or lower eyelids), a unilateral cataract (opacification of the lens of one eye), mental retardation, seizures, and a dysmorphic face is studied genetically. Using FISH (fluorescence in situ hybridization) and MLPA (multiplex ligation dependent probe amplification) analyses, a deletion from between the PAX6 gene and RCN1 gene to the LRRCAC gene is clearly seen. The gene WT1, which was deleted in the 8.5 mb of DNA that the child was missing, is known to cause genitourinary abnormalities and Wilms’ tumor. His lack of this gene and 43 others explain his genital abnormalities, and mild mental retardation. However, the gene PAX6, which causes aniridia and eye problems, was intact, so his cataract and ptosis were not explained. It is thought that some of the 44 genes deleted work alongside PAX6 and the deletion of these genes caused his cataract and ptosis. (Almind, et al., 2009; Redeker, et al., 2008; Tyagi, et al., 2008) Although a small percentage (~.7%) of people has this syndrome, research should still be continued. WT1 and PAX6 genes have already been studied, and they have given answers to some of the symptoms of WAGR syndrome. However, research that is being done on the other genes, like the research made by Tyagi et al, is proving to be very beneficial in our understanding of the other symptoms and cancers. Tyagi’s results give some answers to why WAGR victims are mentally retarded, and he got this from focusing on gene 239FB. The protein constructed from this gene is responsible for fetal development, and the lack of it seems to cause mental retardation. All 7 genes must have some influence on the body, and studying all of the genes may be key to finding answers to WAGR syndrome, and the multiple cancers that also come about from this deletion. (Tyagi, et al., 2008)