Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


WAGR syndrome ... (WAGR syndrome) - Genes BDNF, PAX6 and WT1.

WAGR syndrome is a process that affects many body systems, whose nomenclature comes from its main features: Wilms tumor, aniridia, genitourinary anomalies, and mental retardation.

People with WAGR syndrome have a probability of 45 to 60% of developing Wilms tumor, a rare form of kidney cancer. This cancer is most often diagnosed in children, but sometimes seen in adults. Most people with WAGR syndrome have aniridia, which can cause decreased visual acuity and photophobia. Aniridia is usually the first noticeable sign of WAGR syndrome. In addition, other eye problems such as cataracts, glaucoma and nystagmus can be developed. Referring to genitourinary anomalies, they are observed more frequently in men with WAGR syndrome than women affected. The most common genitourinary anomalies in affected males is cryptorchidism. Women can not have functional ovaries. Women can also have a bicorne shaped uterus, making it difficult to carry a pregnancy to term. Another common feature of WAGR syndrome is intellectual disability. In addition, some affected individuals manifest behavioral or psychiatric problems such as depression, anxiety, attention deficit disorder and hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or autism. Other signs and symptoms of WAGR syndrome may include childhood - onset obesity, pancreatitis, and renal failure. When WAGR syndrome includes obesity starting in childhood, it is often called WAGRO syndrome.

WAGR syndrome is due to a deletion of genetic material on the short arm of chromosome 11. The deletion size varies between individuals affected. Signs and symptoms of WAGR syndrome are related to the loss of multiple genes on the short arm of chromosome 11. Because of this, WAGR syndrome is frequently described as a withdrawal syndrome contiguous gene. The PAX6 and WT1 genes are always eliminated in people with typical signs and symptoms of the syndrome. Because the changes in the PAX6 can affect eye development, it is believed that the loss PAX6 is responsible for the ocular manifestations of WAGR syndrome characteristics. Pax6 gene may also affect brain development. Wilms tumor and genitourinary anomalies are often due to mutations in the WT1 gene, so it is very likely that deletion of the WT1 gene is responsible for these characteristics in WAGR syndrome.

The PAX6, located on the short arm of chromosome 11 (11p13), belongs to a family of genes that play a critical role in the formation of tissues and organs during embryonic development. Family members of PAX genes are also important to maintain the normal function of certain cells after birth. To perform these functions, the PAX genes encode proteins transcription factors. During embryonic development, it is believed that the protein PAX6 activates genes involved in the formation of the central nervous system and pancreas. Furthermore, it is believed that the protein PAX6 controls many aspects of eye development before birth. After birth, probably Pax6 protein regulates the expression of several genes in many structures of the eye.

The WT1 gene, located on the short arm of chromosome 11 (11p13), encoding a protein necessary for the development of kidney and gonads. Within these tissues, the WT1 protein plays a role in cell growth, cell differentiation and apoptosis. To perform these functions, the WT1 protein regulates the activity of other genes by binding to specific regions of DNA. Based on this action, the WT1 protein is called a transcription factor.

In people with WAGRO syndrome, deletion of chromosome 11 it includes an additional gene, BDNF, located on the short arm of chromosome 11 (11p13). This gene encodes a protein found in the brain and spinal cord called brain-derived neurotrophic factor. This protein promotes neuronal survival to play a role in growth, differentiation and maintenance of these cells. In the brain, BDNF protein is active at the synapse, where communication cell to cell occurs. BDNF protein helps regulate synaptic important for learning and memory plasticity. BDNF protein found in brain regions that control aspects such as eating, drinking, and body weight. Protein probably contributes to the management of these functions. It is likely that the loss of BDNF gene is responsible for obesity in childhood onset in people with WAGRO syndrome. People with WAGRO syndrome may be at increased risk of neurological problems such as mental retardation and autism than those with WAGR syndrome. However, it is not clear whether this increased risk is due to the loss of the BDNF gene or other nearby genes.

Most cases of WAGR syndrome are not inherited, but are due to a chromosomal deletion occurs as a random event during the formation of reproductive cells or early embryonic development. As a result, affected individuals often have no history of the disease in his family. Some affected individuals inherit a chromosome 11 with a deletion of a parent unaffected segment. In these cases, the parent carries a balanced translocation in which no gain or no genetic material is lost. Balanced translocations usually do not cause any health problems; however, they may become unbalanced as they are transmitted to the next generation. Children who inherit an unbalanced translocation may have a chromosomal rearrangement extra or missing genetic material. Individuals with WAGR syndrome who inherit an unbalanced translocation have an absence of genetic material on the short arm of chromosome 11, so they have a higher risk of Wilms tumor, aniridia, genitourinary anomalies , and mental retardation.

Tests in IVAMI: IVAMI performed in detecting deletions in the region 11p13, responsible WAGR syndrome, by quantitative real - time PCR [Real time qPCR].

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).