title: Pigmented ocular fundus lesions and APC mutations in familial adenomatous polyposis.
abstract: BACKGROUND
  Familial adenomatous polyposis (FAP) results from a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5q21. The extracolonic manifestations of FAP include pigmented ocular fundus lesions (POFLS), cutaneous cysts, osteomas, occult radio-opaque jaw lesions, odontomas, desmoids, and extracolonic cancers. POFLS are present at birth in about 80% of patients with FAP and are excellent clinical congenital markers for the disease. We studied the distribution of POFLS by number and APC mutation in families of the Johns Hopkins Polyposis Registry.
  
  
  METHODS
  Of the 51 families with FAP, 42 (82%) had an identifiable APC mutation. We correlated the presence/absence and distribution by 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 three or more, or if at least one family member had three or more lesions.
  
  
  RESULTS
  Fifteen of the 21 families (71.4%) were POFL-positive. Mutations of the APC gene were detected in 15 of the 21 families. Of these, 12 (80%) were POFL-positive. Families with mutations at condons 215 (exon 5) and 302 (exon 8) were POFL-negative. Families with mutations at condons 541, 625, 1055, 1059, 1061, 1230, 1309, 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 APC gene are associated with a POFL-negative phenotype, while those in exons 10 to the proximal portion of exon I5 are generally associated with a POFL-positive
authors.affiliation: Johns Hopkins Center for Hereditary Eye Diseases, Wilmer Ophthalmological Institute, Baltimore, MD, USA.
authors.forename: E I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: J
authors.initials: J
authors.lastname: Apostolides
authors.forename: F M
authors.initials: FM
authors.lastname: Giardiello
authors.forename: A J
authors.initials: AJ
authors.lastname: Krush
authors.forename: S V
authors.initials: SV
authors.lastname: Booker
authors.forename: S R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: I E
authors.initials: IE
authors.lastname: Hussels
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000235:genetics; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002891:Chromosomes, Human, Pair 21; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005654:Fundus Oculi; D017491:Genes, APC / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000473:pathology*; D017354:Point Mutation / Q000235:genetics*; D012164:Retinal Diseases / Q000150:complications* / Q000151:congenital / Q000235:genetics
chemical_list: D005819:Genetic Markers