The Story from the University of Miami group
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With the strong support of the IWSA families, we have completed our studies on 31 patients with
WAGR syndrome in collaboration with Dr. Han at NIH. We have summarized our results and an
article has been accepted for publishing in the journal of Cytogenetic and Genome Research. From
the clinical data collected, it was noted that most of the patients have typical clinical features of
WAGR and many also have behavioral problems including autism. The main purpose of this study
was to find out what has caused mental deficit and autistic features in our WAGR kids. We knew
that the Wilms tumor and genitourinary anomalies are caused by missing a copy of the WT1 gene
and the eye problems are caused by missing the PAX6 gene. However, we did not know what genes
have contributed to the abnormal mental development and/or autism. We used a technology called
microarray based comparative genomic hybridization to study the whole genome with a particular
focus on the WAGR region on chromosome 11. With 40 thousands DNA probes placed on each
microarray, we characterized the chromosome 11 deletions in 31 patients and identified all the genes
involved in each deletion. We found that the size of the deletions was different in each patient,
ranging from 4.9 to 23 million base pairs. The number of genes that were missing varied from18 to
62 with an average of 40 genes. In addition to the WT1 and PAX6 genes, we noted that all the
patients studied lost a copy of a gene called PRRG4 which stands for “transmembrane gamma-
carboxyglutamic acid protein 4”. The majority of them also lost a copy of a gene called BDNF, a
“brain-derived neurotrophic factor” and a copy of another gene, SLC1A2, the “solute carrier family 1
glial high affinity glutamate transporter member 2”. We found that missing a copy of the BDNF and
SLC1A2 genes occurred in patients with autism more often than in those without autism. Because
these genes play important roles in normal development and cognitive functions of the brain, our
studies have suggested that missing a copy of the SLC1A2, PRRG4, and BDNF genes can be the
cause of mental retardation and behavioral problems in WAGR patients. In particular, we have
proposed that the BDNF gene may modulate the risk of autism in WAGR patients because this gene
is regulated by a gene called MECP2. This simply makes sense as mutations of the MECP2 gene
causes Rett syndrome which is also associated with autism.
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*Abstract available at PubMed:
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