Genotype/phenotype correlations in aniridia.
OBJECTIVE
To detect and characterize mutations in cases of familial and sporadic aniridia in Maritime Canada, and to look for indications of genotype/phenotype correlation within the cohort.


METHODS
Twelve consecutive and unrelated patients (probands) who had total or nearly complete absence of irides, and four affected relatives, were recruited from Maritime Canada. Clinical data were obtained by chart review and electroretinogram testing. Mutations in the PAX6 gene were detected by single-strand conformation polymorphism and characterized by sequence analysis.


RESULTS
Eleven different PAX6 mutations, 10 of which are novel, were found. The four patients with congenital cataracts all had mutations in the C-terminal proline-serine-threonine (PST)-rich domain of the PAX6 protein. Electroretinograms of nine of 11 patients displayed depressed scotopic maximum response b-wave amplitudes. The greatest decrease in b-wave amplitudes was seen in patients in whom the paired domain was disrupted by mutation.


CONCLUSIONS
Some aspects of the phenotype of aniridia appear to correlate with the predicted effect of point mutations on the paired and PST domains of the PAX6 protein.
Gupta
S K
SK
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
De Becker
I
I
Tremblay
F
F
Guernsey
D L
DL
Neumann
P E
PE
D000293:Adolescent; D000328:Adult; D015783:Aniridia / Q000235:genetics* / Q000473:pathology; D002170:Canada; D002386:Cataract / Q000151:congenital; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D014792:Visual Acuity
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins