Guillespie syndrome ... (Gillespie syndrome) - Gen PAX6.

Guillespie syndrome is a disorder involving ocular abnormalities, ataxia and mild to moderate intellectual disability. This disease is characterized by aniridia. The most affected people have partial aniridia in both eyes, although in some individuals the partial aniridia affects only one eye, or have complete aniridia in one or both eyes. The absence of all or part of the iris can cause decreased visual acuity and increased photophobia. In addition, these individuals may have nystagmus. For its part, the problems of balance and movement in Guillespie syndrome are due to hypoplasia. This anomaly can lead to delayed development of motor skills such as walking. In addition, the difficulty in controlling the muscles of the mouth can cause delayed speech development. The overall coordination difficulties become evident in early childhood when the individual learns these skills. Usually people with Guillespie syndrome continue to have problems walking and speech. However, problems do not worsen over time, and in some cases improved slightly. Other features may include abnormalities in the vertebrae and cardiac malformations.

This process is due to mutations in the PAX6, located on the short arm of chromosome 11 (11p13). This gene 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 encoding proteins which act as 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. Inside the brain, PAX6 protein is involved in the development of olfactory bulb. 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.

They have identified at least 2 mutations in the gene PAX6 people with Guillespie syndrome. Associated mutations inhibit protein coding PAX6 or generate encoding a nonfunctional protein which is unable to bind to DNA and regulate the activity of other genes. Functional protein deficiency disrupts embryonic development, especially the development of the eyes and brain, leading to the signs and symptoms of Guillespie syndrome.

In some cases, the disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. Some affected individuals inherit the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family. However, Guillespie syndrome can also be inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Guillespie syndrome by complete PCR amplification of exons PAX6, and subsequent sequencing.

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).