Congenital Hypertrophy of the Retinal Pigment Epithelium and <i>APC</i> Mutations in Chinese with Familial Adenomatous Polyposis

Abstract

Mutations in the adenomatous polyposis coli gene (APC) often cause both congenital hypertrophy of the retinal pigment epithelium (CHRPE) and familial adenomatous polyposis (FAP). To investigate the relationship between APC mutations, CHRPE and FAP, all FAP patients at the Prince of Wales Hospital, Hong Kong, were asked to participate in a study. Ten Chinese patients from 6 kindreds and their family members volunteered, along with 12 healthy control subjects selected among hospital visitors and staff. All were examined for dilated fundus by indirect ophthalmoscopy. Mutations in APC coding exons were detected by sequencing. In one FAP patient, a novel A insertion at codon 1023 was detected. Three previously reported mutations were detected in 6 FAP patients: a deletion of ACAAA at codon 1061, and 2 truncating point substitutions at codons 216 and 283. In 3 FAP patients, no APC mutation was found, suggesting that mutations in APC coding regions are not the sole cause of FAP or CHRPE. A total of 64 CHRPE lesions were found in FAP patients and some relatives with and without APC mutations. Contrary to most reports, APC mutations before exon 9 did cause CHRPE lesions, albeit relatively few.

Genetic Analysis of the APC Gene in Taiwanese Familial Adenomatous Polyposis

“…The mutation rates in the APC gene vary among different ethnic groups. Further comparison of Chinese ethnic groups from different areas showed that our result in Taiwanese was similar to that from Hong Kong (50%), but lower than that from Singapore (68%) [5,26]. In contrast to the Hong Kong report and our study, which included exclusively ethnic Chinese, the study from Singapore included some patients from different ethnic groups.…”

Somatic APC mosaicism: an underestimated cause of polyposis coli

“…Four of the somatic mosaics had a relatively mild polyposis phenotype (cases 3, 4, 7 and 10), whereas in the literature and from own observations the respective germline APC mutations (p.Arg216X, p.Arg283X and p.Thr1023fs) have been associated with florid forms of FAP 19 29. The germline mutation in case 8, p.Ser1436fs, has not been reported before to our knowledge, but is predicted to be associated with typical or even severe polyposis 30 31.…”

Differential occurrence of mutations causative of eye diseases in the Chinese population

“…In our study of 10 Chinese FAP patients from six kindreds, a novel A insertion at codon 1023 leading to a stop codon was detected in one patient [Pang et al, 2001b]. In six FAP patients three previously reported mutations were detected: a deletion of ACAAA at codon 1061, and two truncating point substitutions at codons 216 and 283.…”

“…In one study, 22 out of 28 FAP families had an APC mutation, and the 1398-1403del deletion was a possible hot spot among Chinese patients [Cao et al, 2000]. We have a similar proportion of FAP patients without a detectable APC mutation, three out of 10 [Pang et al, 2001b]. Perhaps mutations in noncoding APC regions or other genes contribute to FAP or CHRPE.…”