A NOVEL DELETION AT CODON-441 OF THE APC GENE ASSOCIATED WITH OPHTHALMIC LESIONS (CHRPE) IN A SOUTH-AFRICAN FAMILY

A novel mutation at codon 441 in exon 10 of the adenomatous polyposis coli (APC) gene was identified in a South African family of mixed ance stry, using a convenient, non-radioactive, heteroduplex-SSCP screening assay. This single thymidine deletion after nucleotide position 1322 creates a frameshift resulting in a downstream stop codon at amino aci d residue 453 of the APC gene. Genotypes of nine family members were s ubsequently congenital hypertrophy of the retinal pigment epithelium ( CHRPE), since expression of this common extracolonic manifestation of FAP is largely determined by the length of the truncated protein. CHRP E was absent in the five unaffected family members analysed, while fou r mutation positive subjects showed these ophthalmic lesions. Correlat ion between the molecular analysis and ophthalmic examinations, perfor med without knowledge of clinical and genetic status respectively, pro vided additional evidence in favour of the view that the range of phen otypic expression in FAP may result from different allelic manifestati ons of APC mutations.