Peters types I and II, Anomaly ... (Peters Anomaly) - Genes PAX6, PITX2, FOXC1 and CYP1B1
Peters anomaly corresponds to a congenital, uni- or bilateral involvement of the anterior part of the eye characterized by abnormal development of the anterior segment resulting in incomplete separation of the cornea iris or lens.
The phenotype of these patients is very variable. The essential fact is congenital corneal opacity. The size and density of the opacity varies from slight opacity of the corneal stroma to a dense and opaque core leucoma. Corneal opacity may occur alone or accompanied by other less frequent ocular abnormalities: microcornea, microftalmus, flat cornea, sclerocornea, colobomata, angular and iris dysgenesis, ptosis, or hypoplasia of the optic nerve. In most cases, Peters anomaly is bilateral, although the level of impaired vision may be different in each eye. They described two types of anomaly Peters, distinguished by its signs and symptoms. Peters anomaly type I is characterized by incomplete separation of the cornea and iris and mild to moderate corneal opacity. Meanwhile, type II is characterized by incomplete separation of the cornea and lens and severe corneal opacity that can involve the entire cornea.
This may be due to mutations in at least four genes identified: PAX6, PITX2, FOXC1 and CYP1B1. The FOXC1, PAX6, and PITX2 genes are all members of one family homeobox genes that direct the formation of many parts of the body. These three genes are involved in the development of the anterior eye segment. The CYP1B1 gene encodes an enzyme which is active in many tissues, including the eye. The role of the enzyme in these tissues is unclear, but is likely involved in anterior segment development. In many individuals with Peters anomaly, no mutation identified in any of these four genes. In these cases, the cause of the disease is unknown.
The CYP1B1 gene, located on the short arm of chromosome 2 (2p22.2), encoding an enzyme family member cytochrome P450 enzyme. These enzymes are involved in many processes in the body, such as help with drug reactions that break down and produce lipids. CYP1B1 enzyme participates in biochemical reactions in which an oxygen atom is added to other molecules. This enzyme is active in many tissues, including the eye structures. Although not clear , l to enzyme function in eye development, it is believed to play a role in the formation of structures in front of the eye and in the process that regulates the secretion of fluid therein. Have identified several mutations in the CYP1B1 gene related Peters anomaly likely alter the normal function of the CYP1B1 enzyme or enzymes interrupt coding. As a result, there is a normal enzyme deficiency, which probably disrupts the normal development of the eye, although it is unclear exactly how this deficiency leads to the characteristics of the anomaly Peters. CYP1B1 mutations have been associated with glaucoma Peters anomaly.
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. At least 2 mutations have been identified in the PAX6 gene in people with Peters anomaly. These mutations reduce the ability of the protein PAX6 to bind to DNA, altering its role as a transcription factor. As a result, the normal development of the eye deteriorates, leading to the characteristics of the anomaly Peters. Mutations PAX6 causing Peters anomaly can cause other eye disorders related to members of the same family.
The PITX2 genes located on the long arm of chromosome 4 (4q25) and FOXC1, located on the short arm of chromosome 6 (6p25), encode proteins transcription factors. These transcription factors are active before birth in eye development and elsewhere in the body. These proteins play a critical role in early development, particularly in forming structures of the anterior segment of the eye. These structures include the iris, the lens and cornea. It is believed that these proteins may also have roles in the adult eye, such as helping cells respond to oxidative stress. These proteins are also involved in the normal development of other parts of the body, including the heart, kidneys and brain.
It has identified at least one mutation in the gene PITX2 related Peters anomaly. This mutation (IVS3AS, A> T, -2) alters the way in which protein is encoded PITX2, it is believed that interrupts the regulation of cell movement to its proper location in the anterior segment development. Meanwhile, they have been described at least two mutations in the FOXC1 gene in affected individuals. These genetic changes alter the ability of the protein to regulate expression of genes that play a role in the development of the iris, cornea and other anterior segment structures. In addition to Peters anomaly, mutations of PITX2 normally associated with Axenfeld-Rieger syndrome, iridodisgenesis and hypoplasia of the iris. FOXC1 mutations are often associated with dysgenesis of iris and Axenfeld-Rieger syndrome.
Most cases are sporadic Peters anomaly, meaning that occur in people with no apparent history of the disease in your family. In many of these sporadic cases the genetic cause of the disease is unknown. However, some of these cases are caused by a new mutation in one of the above or the inheritance of a mutation of genes unaffected parents. In rare cases, alteration (or related eye disorders) have been described in several members of the same family. Either sporadic or hereditary, when Peters anomaly is due to mutations in the CYP1B1 gene, follows an autosomal recessive pattern of inheritance, 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. When Peters anomaly is due to mutations in the FOXC1, PAX6 or PITX2 gene is inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the process.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Peters anomaly, by complete PCR amplification of the exons of PAX6, PITX2, FOXC1 and CYP1B1 genes, respectively, 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).