Congenital hypertrophy of the retinal pigment epithelium and APC gene mutations in familial adenomatous polyposis

CP Pang 1, JWY Keung 1, NLS Tang 2, DSP Fan 1, JWY Lau 3, L Baum 1, DSC Lam 1.

1Department of Ophthalmology & Visual Sciences, 2Department of Chemical Pathology, 3Department of Surgery, the Chinese University of Hong Kong, Hong Kong, China.

Mutations in the tumour suppressor adenomatous polyposis coli gene (APC) are the cause of familial adenomatous polyposis (FAP). APC mutations between exon 9 and codon 1444 of exon 15 are usually associated with bilateral Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE). We studied 10 Chinese FAP patients from 6 kindreds and their family members. We detected a novel A insertion at codon 1023 leading to a stop codon and 3 previously reported mutations in 6 FAP patients: a deletion of ACAAA at codon 1061, and 2 truncating point substitutions at codons 216 and 283. Variable numbers and types of CHRPE were found in FAP patients and their relatives with and without APC sequence aberration. CHRPE was detected in all our FAP patients. There was a clear association between specific APC mutations and the type of CHRPE lesion. R216X, 3067-3068insA, and 3183-3187del carriers had mainly CHRPE types A and B, while R283X carriers had B and E. Our findings also add to the exceptions that APC mutations before exon 9 can also cause CHRPE. Since no APC mutation was found in 3 FAP patients, mutations in non-coding regions or even other genes may contribute to FAP or CHRPE. But APC sequence aberration may not be the sole factor responsible for development of FAP or retinal lesions. The presence of CHRPE or APC mutations alone may not provide sufficient sensitivity and specificity as a pre-symptomatic marker for FAP. Furthermore, mutations in the coding regions of APC do not necessarily occur in FAP. We suggest combined use of APC mutation screening and CHRPE detection for pre-symptomatic diagnosis of FAP.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Familial and Hereditary Cancer.