Introduction - what is aniridia: Epidemiology, clinical features and genetic implications

Aniridia is characterized by congenital hypoplasia of the iris and alterations of other structures of the eye, including cornea, crystalline lens, optic nerve, and retina. Patients suffer from early onset of nystagmus, photophobia, amblyopia, and severely decreased visual acuity. In 70 % of cases, aniridia is inherited in an autosomal dominant fashion, while it is sporadic in about 30 % of cases. In the great majority of patients, this disease is caused by heterozygous mutations in the PAX6 gene, which encodes for a transcription factor, very well conserved along phylogeny and critical for eye morphogenesis. Aniridia-causing mutations can be of various types, from single base substitution to large chromosomal deletions. All of them determine a loss of function of the gene. When chromosomal deletions are large and involve the WT1 gene, subjects suffer from the WAGR (Wilm's tumor, Aniridia, Genitourinary abnormalities, mental Retardation) syndrome. Both prenatal or postnatal genetic test is available. It is indicated when isolated or WAGR is present, as well as other eye disorders potentially associated with PAX6 mutations. Genetic testing is useful for differentiating aniridia caused by mutations only in the PAX6 gene from those forms associated with the deletion of contiguous genes

Genetic abnormalities detected in ependymomas by comparative genomic hybridisation

Using comparative genomic hybridisation, we have analysed genetic imbalance in a series of 86 ependymomas from children and adults. Tumours were derived from intracranial and spinal sites, and classified histologically as classic, anaplastic or myxopapillary. Ependymomas showing a balanced profile were significantly (P<0.0005) more frequent in children than adults. Profiles suggesting intermediate ploidy were common (44% of all tumours), and found more often (P<0.0005) in tumours from adults and the spinal region. Loss of 22q was the most common specific abnormality, occurring in 50% of spinal (medullary) ependymomas and 26% of tumours overall. Genetic profiles combining loss of 22q with other specific abnormalities - gain of 1q, loss of 6q, loss of 10q/10, loss of 13, loss of 14q/14 - varied according to site and histology. In particular, we showed that classic ependymomas from within the cranium and spine have distinct genetic profiles. Classic and anaplastic ependymomas with gain of 1q tended to occur in the posterior fossa of children and to behave aggressively. Our extensive data on ependymomas demonstrate significant associations between genetic aberrations and clinicopathological variables, and represent a starting point for further biological and clinical studies