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Total aniridia was found in a 2-month-old baby boy. Otherwise the baby was healthy. Ophthalmological examination of the elder sister, parents and paternal grandparents revealed no abnormalities. There was no consanguinity between the parents. Hence, the aniridia was considered sporadic, and the possibility of Wilms' tumour had to be taken into consideration. The chromosomes of the baby were normal, as judged by conventional cytogenetic analysis. In addition, DNA analysis demonstrated that there was no subchromosomal deletion in band 11p13, spanning the aniridia-Wilms' tumour region. Therefore, we conclude that the genetic defect leading to aniridia is confined to the aniridia locus and that the child has no increased risk of developing Wilms' tumour.

By making use of positional cloning strategies we recently isolated a candidate gene for choroideremia (CHM), which is transcribed in retina, choroid, and/or retinal pigment epithelium. The gene contains an open reading frame that is structurally altered in 10 CHM patients with sizable deletions and in a female patient with a balanced translocation involving the Xq21 band. Employing PCR-SSCP analysis and direct DNA sequencing we have now detected and characterized different point mutations in five patients with CHM. Each of these mutations introduces a termination codon into the open reading frame of the CHM candidate gene, thereby predicting a distinct truncated protein product. Together these findings provide convincing evidence for the candidate gene being identical with the choroideremia gene.

A large family with autosomal dominant aniridia is described. One of the family members presented with reduced visual acuity, nystagmus, slightly distorted macular reflex, but normal irides and clear media. Because of the high variability in expression of aniridia, even within family, a diagnosis of aniridia could not be excluded. However linkage analysis using tightly linked chromosome 11p13 markers flanking the aniridia locus (catalase, D11S151, and D11S325) made it highly unlikely that this patient inherited the aniridia gene from his affected mother.

DNA diagnosis of X-linked retinitis pigmentosa (XLRP) is hampered by its genetic heterogeneity, while a clinical subdivision is almost impossible to make. So far, diagnostic services have been offered only to those families in which linkage to one RP locus (RP2 or RP3) has been clearly established. In most families, however, the nature of the XLRP type cannot be distinguished on the basis of linkage analysis. Here the authors describe that in some families DNA diagnosis is nonetheless feasible, when polymorphic DNA markers are used which span the entire Xp21.1-Xcen region and when no recombination between these markers disturbs the phase.

X-linked juvenile retinoschisis usually results in a rather serious visual handicap in affected males. However, occasionally patients can present with very subtle clinical signs without subjective complaints. For this reason, the family history can be misleading and caution is necessary when analysing the pedigree and giving genetic advice. In this report a family with X-linked retinoschisis is described in which segregation analysis with DNA probes strongly suggests that the deceased grandfather, who was said to have had good vision, had been affected by juvenile retinoschisis.