More information also available on:Aniridia Europe

Medical info - genetics

This report is based on an interview with an ophthalmologist and doctor in genetics of the University Hospital of Ghent (Belgium). In this interview he stipulated a clear view on the main principles of genetics - and more specific Pax 6 mutations – and its impact on molecular biology. These guiding principles were further completed with self-study research of scientific information available on the Internet. We did an attempt to explain it in simple words to make this rather technical complicated subject more understandable for every person. By this report we aim to provide you with some concise genetic background information on Aniridia, caused by Pax 6 mutation, and the impact on stem cells and other molecular biology.

Principles of genetics and molecular biology

Each cell has its own function(s) and form, depending on where they are located into the body. These functions or biological processes are only possible with the necessary proteins. The recipes for those proteins are contained by the DNA (present in the core of each cell). A gene is a DNA-code which contains the recipe for one particular protein. Near by the gene there is a DNA-code functioning as a promotor, more specific the one stipulating which kinds of cells will produce the respective protein, the quantity of it and its frequency. As a consequence one cell will only produce a limited number of proteins, depending on its characteristics and on its micro-environment. In fact the promotor’s activity depends on a variety of both external and internal variables and consequently will take into account, amongst others, the cell’s micro-environment.

It is important to know that each cell contains two copies of almost every gene (except a few derogative genes).

Most cell’s life cycle is limited. They are multiplied (generally only when necessary) by dividing. The cell is divided into two so-called ‘daughter cells’. These daughter cells may be different from the original cell (‘the mother cell’) and even from each other. This is because, depending on the cell’s environment and signals it receives from the environment, different genetic programs may be set on, resulting in a different cell than the ‘mother cell’ (ca. 220 different phenotypes). As far as known each cell is the same during embryonic development (embryonic stem cells^1) and they are differentiating (adopt properties according to their position) whilst the embryonic formation (specialized cells).

A stem cell is defined as a cell with the ability to self-renewal (by cell division) and with the potential to differentiate into the phenotype of another tissue. Some specialized cells preserve the ability to differentiate (plasticity) but only into certain phenotypes (so-called adult stem cells^2: e.g. cells of bone marrow).

In the meantime there are even indications to believe there might be cells into the human body, being not or very little specialized.^3

Almost every cell is “terminal differentiated”, which means they lost their ability to be divided and to differentiate (e.g. nerve and kidney cells). When those kind of cells are damaged, they are no longer headed which leads to a reduction of their functioning. If doctors had the disposal of cells with the ability to replace the damaged cells, they would have been able to treat a lot of patients – which in these days have to be helped partially in an alternative way.

From fertilized ovule to embryo

The origin of these cells?

The fertilized ovule (female egg united with male sperm) is ‘the mother’ of all body cells. The fertilized ovule contains DNA inherited from both parents and are constructed into 2 spirals (double helix) which are twisted in each other like 2 cork triggers which are screwed in each other. The ‘mother cell’ is divided into 2 ’daughter cells’, then into 4 and so on. Before each cell division, the DNA is multiplied (copy of the both torsels), so that each ‘daughter cell’ will have the same genetic material like the original ‘mother cell’. During such replication (taking a copy) a mutation occurs within the copy of the Pax 6 gene (either in the mother’s ovule or in the father’s sperm cell ^4). Due to the successive cell divisions, this mutated copy has developed through the baby’s whole body (thus 1 mutated copy and 1 good copy of Pax 6 in each cell of the body). So you can indeed notice that the sporadic mutation in fact occurs before the fertilization.

Till now ca. 300 different Pax 6-mutations are already registered within aniridia patients and the intensity and nature of the disorder’s phenomena could vary according to the respective mutation. In my individual case the mutation has not yet been detected in other aniridia patients, although it is similar to mutations found in other aniridia patients.

Genotype – phenotype correlations

Isolated aniridia. PAX6 missense mutations (often in the paired domain) tend to produce atypical or variable-phenotype aniridia or related disorders (see subsection below) such as foveal hypoplasia, autosomal dominant keratitis, developmental abnormalities of the optic nerve.

PAX6 haploinsufficiency through loss-of-function intragenic mutations (often premature termination codons), larger deletions, or occasional chromosomal rearrangements at nearby regulatory elements produces classic aniridia [Kleinjan & van Heyningen 1998, Prosser & van Heyningen 1998, Gronskov et al 1999, Hanson et al 1999, Lauderdale et al 2000, van Heyningen & Williamson 2002, Chao et al 2003, Tzoulaki et al 2005, Dansault et al 2007].

Although the phenotype can be variable within a family, individuals usually show little difference between the two eyes. The causes for this variation in phenotype among individuals with the same mutation are unknown [Negishi et al 1999].

Other Ocular Phenotypes Caused by PAX6 Mutations

  • Keratitis: Limbal stem cell deficiency with vascularization and opacification of the cornea ± foveal hypoplasia
  • Microcornea: Small corneas with diameters <10 mm
  • Peters anomaly^5: Central corneal opacity caused by iridocorneal adhesions or lenticulocorneal adhesions. Glaucoma in 50%
  • Ectopia pupillae: Pupil displaced from center of iris
  • Juvenile cataracts: Early-onset lens opacities
  • Isolated foveal hypoplasia: Normal iris, reduced foveal reflex, reduced macular pigmentation, retinal vessels crossing the usually avascular foveal zone
  • Optic nerve aplasia/hypoplasia or coloboma: Small, absent, or malformed optic nerve heads
  • Microphthalmia, cataract & nystagmus: Very small eye, early lens opacities, glaucoma common
  • Foveal hypoplasia/macular coloboma with neurodevelopmental anomalies: Absent or highly malformed central chorioretinal area, variable neurologic abnormalities (e.g., cerebellar syndrome, cortical atrophy, low IQ, absent pineal gland)


The prevalence of aniridia is 1:40,000 to 1:100,000. No racial or sexual differences are recognized.

Maturing-process of stem cells

  1. Embryonic Stem cell
  2. Foetal Stem cell
  3. Adult Stem cell
  4. Progenitor cell
  5. Precursor cell

There are as well blood making as tissue making stem cells.

Further reading - useful links


^1: In other words. embryonic stem cells are pluripotent (may result into all human tissues)

^2: In other words adult stem cells are multipotent (may result into certain human tissues, thus not all). The differentiation mode may be re-programmed. An adult stem cell is a non-differentiated or non-specialized cell, which exists in a differentiated and specialized tissue and which may result into all mature cells of the respective tissue, isolated from (e.g. corneal stem cells). For the maturing process of stem cells: see the last but one section.

^3: see link related to stem cells (in Dutch)

^4: In the case of a heterozygoteous mutation, in each cell there is one good copy and the other one is mutated. In the case of a homozygoteous mutation both copies are mutated.

^5: PAX6 mutations have not been detected in most individuals with Peters anomaly [Churchill et al 1998, Chavarria-Soley et al 2006, Dansault et al 2007].

Author: Joeri Van den Bosch