Pigmented ocular fundus lesions and APC mutations in familial adenomatous polyposis

Abstract

Background Familial adenomatous polyposis (FA P) results from a germline mutation in the adenomatous polypsis coli (APC) gene on chromosome 5q21. The extracolonic manifestations of FAP include pigmented ocular fundus lesions (POF LS), cutaneous cysts, osteomas, occult radio-opaque jaw lesions, odontomas, desmoids, and extracolonic cancers. P O F L S are present at birth in about 80% of patients with F A P and are excellent clinical congenital markers for the disease. We studied the distribution of POFLS by number and A P C mutation in families of the Johns Hopkins Polyposis Registry. Materials and methods Of the 51 families with FAP, 42 (82%) had an identifiable A P C mutation. We correlated the presence/absence and distribution by number of POFLS with the type and location of the mutation in the A P C 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 A P C gene had been undertaken. Families were considered PoFL-positive if the average number of lesions per patient was three or more, or if at least one family member had three or more lesions. ResuZtsFifteen of the 21 families (71.4%) were PoFL-positive. Mutations of the A P C gene were 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 at codons 541, 625, 1 o~~ , 1 o~~, 1 0 6 1 , 1 2 3 0 , 1~o~, 1465, and 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 and the distal portion of exon 15 of the A P C gene are associated with a PoFL-negative phenotype,while those in exons 10

A Unique Presentation of Grouped Congenital Hypertrophy of the Retinal Pigment Epithelium

“…Mutations in the first eight exons of the gene result in polyposis in the absence of POFLs, whereas mutations in exons 9-15 are associated with polyposis and concomitant expression of POFLs. 13,14 In summary, the various forms of CHRPE can be distinguished from the POFLs based upon their characteristic clinical features. The ophthalmologist assumes an important role in differentiating the two entities.…”

Germinoma presenting as a fourth cranial nerve palsy in a patient with adenomatous polyposis coli (APC) gene mutation

“…These characteristic fundus lesions are thought to occur in up to 80% of patients with APC mutation. 5 They may be present at birth, with no malignant potential. 5 We found one such lesion in each eye of our patient.…”

“…5 They may be present at birth, with no malignant potential. 5 We found one such lesion in each eye of our patient. Traboulsi and colleagues 6 demonstrated that multiple patches of pigmented ocular fundus lesions are a clinically useful predictor of colorectal polyposis.…”

Pigmented and depigmented lesions of the ocular fundus

“…There is a thickening of Bruch's membrane under the focal lesions. Mutations in exons 1-8 are associated with a POFL-negative phenotype, whereas those in exons 10-15 are generally associated with a POFL-positive phenotype [65][66][67]. These authors also proposed that POFLs are best classified as adenomas of the RPE.…”