Pigmented ocular fundus lesions (POFLS) and APC mutations in familial adenomatous polyposis

Purpose: Familial adenomatous polyposis (FAP) results from a germline mutation in the adenomatous polyposis coli (APC) gene on 5q21. The extracolonic manifestations of FAP include POFLs, cutaneous cysts, osteomas, occult radio-opaque jaw lesions, odontomas, desmoids, and extracolonic cancers. We studied the distribution of POFLs by number and mutation in families of the Johns Hopkins Polyposis Registry. Methods: 42 of 51 (82%) families with FAP had an identifiable APC mutation. We correlated the presence and number of POFLs with the type and location of the mutation in the APC gene in 21 families where an ocular examination had been performed in at least one affected member, and where a systematic search for mutations in the APC gene had been undertaken. Families were considered POFL-positive if the average number of lesions per patient was 3 or more. Results: 15 of the 21 families (71.4%) were POFL-positive. Mutations of the APC gene could be detected in 15 of the 21 families. Of these, 12 (80%) were POFL-positive. Families with mutations at codons 215 (exon 5) and 302 (exon 8) were POFL-negative. Families with mutations in codons 541, 625, 1055, 1059, 1061, 1230, 1309, 1465, 1546 (exons 12-15) were POFL-positive. One patient with a mutation at codon 2621 (exon 15) had no POFLs. Conclusions: Mutations in exons 1-8 of the APC gene are associated with a POFL-negative phenotype, while those in exons 10-15 are generally associated with a POFL-positive phenotype. Mutations at codon 2621 may result in no ocular lesions.