Genetic background of aniridia.

 Aniridia( 80%) occurs due to a defect in the gene PAX6, which is located in the upper  part (short arm) of the 11th chromosome. ( This chromosome has two divisions known as "p" and q" arm;the 'p' arm  is shorter, and the "q" arm is longer). Pax6 gene regulates the development of the eye, central nervous system, and also pancreas and intestine. Changes in the Pax6 gene may lead to a significant loss of visual acuity and a many of ophthalmic diseasese.  People with aniridia may also have defects of the nervous system, they may often  suffer metabolic disorders such as obesity and other metabolic problems.
Pax6 geneis  dominantly inherited, and this means that one copy of an abnormal gene is sufficient to cause a  disease. If  both  copies  are abnormal, then it leads to severe disease. A child can die at birth or it may have severe abnormalities, such as  lacking  an eye, ears or having defects of the nose, ears, underdevelopment of the brain, the anomaly of the skull bones. Pax6 gene mutation may be expressed either in the complete absence of the 11th chromosome that contains  gene Pax6; or it can change the components of the gene that in turn disrupts its normal functioning.

Each person has two copies of each gene. One copy is inherited  from the mother and one from the father. If one  copy  is normal  and  the other is  abnormal, but  person is healthy , the gene shows a recessive mode of inheritance. This means that a single copy of an abnormal gene is not enough to cause a disease. If  a  person has one normal copy and one abnormal, and he(she)  has a disease, the gene shows the dominant pattern of inheritance. This means that a single copy of  an abnormal gene is sufficient to cause  a disease.

There are 4  types of  aniridia depending on the type of inheritance:
Familial Aniridia (Autosomal Dominant)
This is the most common form of Aniridia. It is inherited directly from a parent who has Aniridia themselves. It is the result of a mutation in a PAX6 gene. Familial Aniridia is associated with many serious ocular (eye) conditions, including cataracts, glaucoma, and corneal pannusA close follow-up by an experienced ophthalmologist is very important.  Each child  whose parent has  familial Aniridia will have a 50% chance of inheriting the gene mutation.

-  Sporadic Aniridia (no deletion detected)
This type of Aniridia is the second most common form. Both parents have normal chromosomes. The affected person has a “new” mutation of  PAX6 gene (a mutation which occurred before or very soon after conception) It is not known what causes this mutation. People with sporadic Aniridia are at risk for the same eye complications as those with Familial Aniridia. Children with sporadic Aniridia should also be carefully followed for the development of Wilms tumor, regardless of the results of genetic testing.
People with Sporadic Aniridia have a 50% chance of passing on this condition to their children.

-WAGR syndrome - a new kind of sporadic aniridia(deletion of 11p13)                                                                                    This type of Aniridia is rare. Approximately 30% of people who are born with Sporadic Aniridia will also have WAGR syndrome.  Both parents have normal chromosomes.

 WAGR syndrome has a  mutation of  Pax6 gene with  some of the neighboring genes mutation in the short arm of the 11th chromosome. People with WAGR syndrome have a contiguous gene deletion (a missing  part of a gene ), which contains  PAX6 gene, and the nearby region of 11p13, which contains a gene, called the Wilms'  tumor suppressor gene or gene WT1. The  absence of a WT1  allele in  these people leads  to a  high risk  ( 45%) of  Wilms'  tumor  mutation. In  Wilms tumor patients, usually (86% )  have only one kidney affected, in 6% both kidney, 8% of patients have mamy  tumors  in one kidney. Early diagnosis of the syndrome, along with close medical supervision and educational support will help the child to reach their best potential.

Children with WAGR, can be identified, except for aniridia and Wilms' tumor, anomalies such as malformations of the genitourinary system, and mental retardation. Cytogenetic studies have shown that these patients have a deletion of the short arm of chromosome 11, which always includes the area 11p13. It was found that the deletion in this syndrome is defined by adjacent genes, including the gene aniridia - Pax6 gene, Wilms' tumor suppressor - WT1, gene enzyme catalase, etc.

   Two genetic tests are required to check for WAGR syndrome. One is called the “Karyotype”, which is a basic examination of the chromosomes. The second test is called a “FISH” probe. The FISH probe is a very detailed examination of the WAGR-related portion of chromosome 11.

Karyotyping - a diagnostic study of the structure and the number of sets of chromosomes (karyotype). Karyotyping blood eliminates the possible genetic problems the couple may have. Thus, in some countries it is common to do this analysis all before marriage.

The normal female karyotype shows 46 chromosome 46 XX, and a normal male karyotype 46 XY. This standard analysis of chromosomal material evaluates the quantity and structure of the chromosomes up to 99.9%. Analysis of chromosomes  typically made from blood (white blood cells), prenatal sample skin biopsies and other samples.

In some cases, this study is not enough to issue a report on the karyotype. In these cases, the use of molecular cytogenetic techniques, in particular fluorescent hybridization (FISH).  "Fish" probe can detect a more subtle structure of individual regions of certain chromosomes; it can quickly investigate any chromosomal site in different tissues (organs). Fish probe allows a very detailed examination  of the  11 chromosome, which are connected with the WAGR syndrome. This new technology that is used to detect mutations in the 11th chromosome that contains PAX6 gene.

Both tests are carried out from a blood sample.

In Russia, the  aniridia gene analysis can be performed by Hlebnikova Olga Vadimovna, MD, an ophthalmologist and a clinical geneticist  at Russian Academy of Medical Sciences, Medical Genetics Research Center , Moscow.

For more information about WAGR syndrome, please see the website:

-Gillespie Syndrome (Autosomal Recessive)
This type of Aniridia is extremely rare. It may be inherited through parents who do not have Aniridia themselves, but who both have one normal copy of the PAX6 gene, and one mutated copy. This type of Aniridia is associated with a particular appearance of the iris remnant (described as having a “scalloped” border) mental retardation, and cerebellar ataxia, (muscle incoordination).

The risk  of  the  child  with aniridia to have siblings  with aniridia  depends on the genetic status of the parents of the child.  If the parents of the child with aniridia have an isolated aniridia or mutation in  Pax6 gene, the probability of  the  diseases is 50%. If the parents do not have this mutation, the chance to getting sick is very low.  Each child with isolated aniridia may inherit a mutation of  Pax6 gene and developing aniridia with a probability of 50%.

Dr. Elizabeth Simpson from Canada and Dr.James Lauderdale from USA  working  hard now on aniridia gene therapy – a method to overcome PAX6 mutations.