H.sapiens oculorhombin (aniridia) mRNA, complete cds.
Accession Number M77844
Retro illumination in
Aniridia showing absence Direct
illumination of an eye Direct
illumination of a normal
of iris, the edge of the lens is clearly visible with Aniridia. eye with dark iris for comparison
Aniridia in Greek literally means "without iris" and it is a congenital, hereditary, bilateral extreme form of Iris hypoplasia. Aniridia is caused when the gene responsible for eye development that is Pax6 does not function correctly, this causes the eye to stop developing too early and when the baby is born most of the eye is underdeveloped to some degree (Aniridia Network). Aniridia also has corneal, lens, optic nerve and retinal manifestations. it may also cause foveal and optic hypoplasia. Vision becomes progressively worse later in life, which in turn results in cataract, glaucoma, nystagmus, aniridic keratopathy, amblyopia, micro cornea (small cornea), stabismus (cross eyes) and other diseases such as dysosmia, dysnomia, glucose intolerance, WAGR and Gillespie syndrome. Aniridia occurs as the following (Aniridia)
According to the article Aniridia by Daljit Singh at present, Aniridia affects about 1 in 60,000 individuals; in US that would be 1 in every 90,000 individuals, therefore based on our current population that would be about 2945 individuals; in Canada that would be about 475 individuals based on their current population. Internationally however Aniridia is rare and has an incidence rate of about 1 every 64,000 to 1 per 96,000 births ( 2/3 are familial).
More Pictures from Aniridia by Dr.Daljit Singh and more pictures from Aniridia in the Newborn by Dr.Sophie Bakri.
Genetic Basis for Disorder:
Aniridia is a disease caused by the following : (Aniridia)
an identifiable chromosome deletion of the short arm of chromosome 11
patients who have a positive family history for Aniridia. two genetic loci for Aniridia, one ( AN1) on chromosome arm 2p and one ( AN2) on chromosome arm 11
isolated ocular malformation, Aniridia is an Autosomal dominant disorder and is caused by mutation in the PAX6 ( paired box gene family)
Ton CC et all were the first ones to clone this gene. Positional cloning and characterization of a paired box- and homeobox-containing gene from the Aniridia region.
Master map of the gene on sequence .
According to the article Tandem duplication of 11p12-p13 in a child with borderline development delay and eye abnormalities: dose effect of the PAX6 gene product? published in the American journal of medical genetics "PAX6 is not only developed in the retinal, iris, lens and surface ectoderm it is also expressed in discrete regions of the fore, hindbrain, neural tube, the pituitary gland and the nasal epithelium...PAX6 gene not only induces eye development it also causes pancreatic, pituitary, central nervous system development". According to OMIM database the PAX6 gene encodes a transcriptional regulator that recognizes target genes through its paired-type DNA binding domain. this paired domain consists of 2 sub binding domains the N-terminal sub domain ( NTS) and the C terminal sub domain (CTS) these sub domains bind to respective DNA sequences. when about 14 amino acids encoded by exon 5a are inserted into NTS, this abolishes the DNA-binding activity of the NTS and unmasks the DNA-binding ability of the CTS. Thus, exon 5a appears to function as a molecular switch that specifies target genes. According to the article The Pax-6 homeobox gene is expressed throughout the corneal and conjunctival epithelia by BM Koroma et all In cells of the surface epithelia of the adult cornea and conjunctiva the PAX6 may function by regulating structural or secretory specializations and might perform a direct role in the maintenance and proliferation of corneal stem cells, a vital process that appears to be defective in the disease Aniridia. Aniridia is a disease in which the iris fails to form normally and therefore the person concerned might have malfunctioning visual functions The Pax6 gene encodes a transcription factor that is expressed in developing adults of all multi cellular organisms, be it drosophila, mouse or humans. Veronica Van Heyningen from the University of Edinburgh in her article Lessons from imperfect miracles explains that their group identified the PAX6 (paired-box and home box gene) that is specially expressed in the developing eye and brain. The affected individuals carry one dysfunctional and one normal copy of the gene and have about a 50 percent chance of passing the faulty gene to each of their children. PAX6 has turned out to be a key regulator of eye development during the recent studies and the protein made by the PAX6 gene plays a major role in eye and brain development by binding to DNA target sequences and regulating the activity of a cascade of other genes required for these intricate developmental processes, however the mutated version lacks this ability. By studying DNA from volunteers with Aniridia, Heyningen says that they have discovered that most cases are caused by a 50% reduction in PAX6 protein. The amino acid sequence of normal mouse PAX6 protein is completely identical to the human gene product and therefore the small eye mouse abnormality in mouse is a good example for studying the effects of PAX6. In mice the minimal PAX6 gene required for making the protein is 25,000 nucleotides but they had a further 200,000 nucleotides present on each side of the minimal gene. If they reduced this flanking DNA to only 120,000 on one side, they no longer managed to correct the abnormality in a parallel experiment. This demonstrates that the minimal 25,000 nucleotide PAX6 gene requires a lot of additional DNA information outside the protein coding region to regulate correct gene expression. She also discovered that the presence of too many copies of PAX6 is also damaging and causes eye abnormalities.
Azum N, et also
presents another idea in the article
Missense mutations in the PAX6 gene in Aniridia. "Haploinsufficiency
of the gene product is thought to result in the Aniridia phenotype, because most
mutations thus far detected have been large deletions encompassing the entire
gene and nonsense, frame shift, or splice errors that result in premature
translational termination on one of the alleles...".
According to Aniridia Network in a heterozygote form this disease causes atypical Aniridia phenotypes or other eye diseases such as congential nystagmus, isolated foveal hypoplasia, mild or moderate hyposmia, sleep problems ( pineal gland). Unilateral polymicrogyria, pancreatic malfunction and in homozygous form causes craniofacial abnormalities, nerves system defects which are lethal. also causes Gillespie syndrome. The deletion of the band 11p13 will cause miller syndrome to occur and this is patients with sporadic Aniridia developing Wilms tumor (Aniridia in the Newborn).
According to Dr. Bakri (Aniridia in the Newborn) in 1818, Barratta first described Aniridia and this disease is discovered early on in life. Dr Singh gives a very detailed diagnostic process in his article Aniridia and according to him Aniridia can be diagnosed when presented with the following symptoms which would be, absence of iris (trabecular meshwork might be covered partially or completely by iris stump), nystagmus, strabismus, reduced vision, photophobia, cornea ( microcornea, arcus juvenilis, epithelial ulcers, pannus), crystalline lens ( either transparent, opaque or dislocated). Fundus ( optic nerve hypoplasia, macular reflex dull, glaucoma) normal or increased intraocular pressure. Thorough family history is also required including questions about ocular , genitourinary, mental abnormalities, dental anomaly, low vision or protruding umbilicus.
There are several tests that can be done to determine whether one suffers from it or not early on (Aniridia)
chromosomal deletion can be detected by cytogenic testing by using high- resolution banding (Aniridia) that means chromosomal analysis of the patient and the family and genetic analysis of the PAX6 gene should be performed Aniridia in the Newborn
Submicroscopic deletions can be recognized with a fluorescence in situ hybridization (FISH technique)
Serial renal ultrasound examinations
MRI ( imaging of the abdomen and brain specifically) Aniridia in the Newborn
In infants according to Dr Bakri in her article Aniridia in the Newborn an infant might come to medical attention with nystagmus, photophobia, strabismus, amblyopia or something else like an abnormal pupil which might be fixated or dilated.
There are several treatment options out there for people suffering from aniridia:
People suffering from this disease will need a lifelong close regular and careful follow up and will also need a support system to deal with this disease. They will need to be thoroughly educated about this disease so that they can deal with this disease in a better way. reading journals about aniridia might not be very helpful due to the technical language used in these journals or articles that is why there are several organizations out there which provide information to the patient and his/her family member regarding this disease. these organizations not only provide basic information regarding the disease but also provides knowledge about the risks concerning this disease along with procedures, medicines that might help deal with the problem. there are several support websites on the web. a few are named below. (Aniridia Network)
the Mexican Association for Aniridia
Spanish association for aniridia
Aniridia Network UK
USA Aniridia Network
Reaching Out Network WAGR/Aniridia Newsletter
in addition to these websites NORD also lists several organizations related to Aniridia.
Extra Credit Questions:
1. Which gene plays an important role in the disease aniridia ? Aniridia Network
2. Mutation in ____________ causes aniridia ? Aniridia
3. Give a brief description of the syndrome in which patients with sporadic aniridia develop Wilms tumor. Aniridia in the Newborn
NAME- Quratulain Saeed
I give permission to allow Dr. Marrs to post this report on the web as an assignment in an upcoming Biology class, with my name cited as the author
The text of this BLAST project exercise is copyrighted under the name of IUPUI Student Quratulain Saeed 2003, as part of the IUPUI biology course Biotechnology 540. There are no restrictions on its use by educators or by non-profit institutions as long as its content not modified, proper copyright acknowledgement is retained, and this statement is not removed.