What is the risk for other family members?
Isolated aniridia (occurring in the absence of other systemic involvement): The risk of the siblings of the affected child depends on the parents’ genetic status. If the parent has isolated anirdia or has an identifiable PAX6 mutation, the risk is 50%. If the parents are unaffected, the risk is low. Each child of an individual with isolated aniridia has a 50% chance of inheriting the PAX6 mutation and developing aniridia.
WAGR Syndrome: If a parent has a balanced chromosome rearrangement including the PAX6 locus and the adjacent WT1 locus, the risk to other offspring increases. If the affected child has a de novo contiguous gene deletion and neither parent has evidence of mosaicism for the deletion, the risk for other offspring is no greater than that in the general population.
Individuals with WAGR syndrome caused by a cytogenetic deletion generally do not reproduce.
What is haploinsufficiency?
Haploinsufficiency describes the situation in which an individual is affected although having a copy of the normal gene as well as a copy of mutated gene. The single copy of gene is incapable of producing enough proteins for normal function.
More about PAX6
Human PAX6 is on chromosome 11p13 and encodes a 422 amino acid transcriptional regulator. PAX6 is a transcription factor that is required to regulate genes’ expression, and the specified expression pattern is responsible for proper development. The principal sites of PAX6 expression are the eye, the brain, and spinal cord. Mutations in PAX6 may disrupt this pattern and lead to aniridia phenotype.
Theses mutations are summarized in The Human PAX6 Mutation Database. Most of them result in pre-mature translational termination (incomplete amino acid sequence) on one of the two gene copies (allele), and haploinsufficiency of the gene has been suggested to cause aniridia. On the other hand, only a few cases of missense mutations (the amino acid sequence has been altered) has been detected. It has also been reported that mutations in neighbouring regions of DNA also cause aniridia by interfering of PAX6 expression. Such mutations lead to a decreased of functional PAX6 proteins.