Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients

Olschwang, Sylviane; Tiret, Anne; Laurent‐Puig, Pierre; Muleris, Martine; Parc, R; Thomas, Gilles

doi:10.1016/0092-8674(93)90539-3

Cited by 277 publications

(110 citation statements)

References 40 publications

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“…The mutations where no CHRPE manifestations are at 299, 332 and 1428, respectively (Table 1 and Figure 2). This demarcation appears to be consistent with the findings of an earlier study 10 delineating the CHRPE limits to the region between codons 463 and 1387.…”

Section: Genotype-phenotype Correlationsupporting

confidence: 80%

“…6 Mutation in the very 5' and 3' ends of the protein as well as the alternatively spliced sites in exon 9 have been associated with a more attenuated form of FAP. [7][8][9] Truncating mutations between codons 463 and 1387 are associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE), 10 whilst truncating mutations between codons 1403 and 1578 are associated with Gardner's syndrome 11 such as increased desmoids and mandibular lesions but not CHRPE.…”

Section: Introductionmentioning

confidence: 99%

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APC mutation and phenotypic spectrum of Singapore familial adenomatous polyposis patients

Cao

Seow‐Choen

et al. 2000

Eur J Hum Genet

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Familial adenomatous polyposis (FAP) is a familial form of colon cancer caused by mutation of the adenomatous polyposis coli (APC) gene. Although the APC gene has been extensively studied in the Caucasian population, it has not been previously described in the Chinese population. In the present study, we investigated APC mutation and phenotypic spectrum in the Singapore FAP families who are predominantly Chinese. The protein truncation test (PTT) was used to screen the entire APC gene for germline mutations in 28 unrelated families. Fifteen different mutations were identified in 22 families. Eight mutations were 1-11 basepair deletions or insertions; three involved deletions of whole exons and four were nonsense mutations. Nine of the mutations, including two complex rearrangements, are novel. Eight families including three de novo cases have the same (AAAGA) deletion at codon 1309, indicating that like the Western families, codon 1309 is also the mutation 'hot spot' for Singapore FAP families. In contrast, we did not find any mutation in codon 1061, the second hot spot for the Western population. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is consistently associated with the prescribed domain (codons 463 to 1387) and is the only phenotype with no intra-family variation. Other than CHRPE, differences in the type and frequency of extracolonic manifestations within the FAP families suggest the influence of modifying genes and environmental factors.

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Section: Genotype-phenotype Correlationsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

APC mutation and phenotypic spectrum of Singapore familial adenomatous polyposis patients

Cao

Seow‐Choen

et al. 2000

Eur J Hum Genet

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“…Our results, in agreement with most studies, indicate that patients with germline APC deletions show a 'classical' FAP phenotype with more than 100 adenomatous polyps, presence of CHRPE, and onset age of about 25-35 years. 10,11,13,15,18 This indicates that the 'null allele' in patients bearing APC gene deletions and dominant negative alleles are equivalent in respect of their phenotypic consequences. However, the putative dominant-negative mechanism cannot be applied to the 'classical' phenotype observed in patients bearing large deletions.…”

Section: Discussionmentioning

confidence: 99%

“…In some of these patients the colonic manifestations, ie number of polyps, age at onset, and CHRPE, were similar to those observed in classical FAP. [9][10][11][12][13][14][15][16]18 Mental retardation and/or facial dysmorphism have also been described. [10][11][12][13][14] Within these cases the frequency of extracolonic manifestations, including subcutaneous lesions, mandibular osteomata and desmoid tumours, are similar to those observed in FAP induced by other types of mutation.…”

Section: Introductionmentioning

confidence: 99%

Three submicroscopic deletions at the APC locus and their rapid detection by quantitative-PCR analysis

et al. 1999

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We describe three unrelated kindreds, affected by familial adenomatous polyposis (FAP), with 5q submicroscopic deletions that encompass the entire adenomatous polyposis coli (APC) gene and the adjacent DP1 gene. In one family the deletion encompasses also the MCC (mutated in colon cancer) gene. Affected members of these families had dysplastic adenomatous polyps and congenital hypertrophy of the retinal pigment epithelium (CHRPE); no individual was affected by mental retardation or facial dysmorphism. The deletions were detected by linkage analysis with several intragenic and closely flanking polymorphic markers and confirmed by a quantitative PCR analysis. This procedure could have an impact on the detection of the molecular defect in FAP patients in whom mutational analysis fails to identify the specific mutation.

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“…Hence, we searched for truncating APC mutations in all coding sequences from exon 9 to the termination signal at the 3' end of exon 15, which includes all regions of APC known to be associated with expression of the CHRPE phenotype in FAP (Olschwang et al, 1993). Peripheral blood from all 33 patients exhibiting AEM was screened by an in vitro synthesised protein assay (IVSP) (Powell et al, 1993;Prosser et al, 1994) for translation-terminating APC gene mutations and by heteroduplex analysis (Prosser et al, 1994;Keen et al, 1991) for each of exons 9 -14.…”

Section: Apc Gene Screeningmentioning

confidence: 99%

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer

Dunlop

Farrington²,

Bubb³

et al. 1996

Br J Cancer

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Summary We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM 1985a, b; Houlston et al., 1992; Dunlop, 1983; Hunt et al., 1994). These features, congenital hypertrophy of the retinal pigment epithelium (CHRPE) and mandibular osteomas, occur in 90% and 75% respectively of patients with classical FAP (Utsunomiya and Nakamura, 1975;Bulow et al., 1984; Traboulsi et al., 1987;Berk et al., 1988;Chapman et al., 1989;Giardiello et al., 1991; Hodgson et al., 1994;Wallis et al., 1994). The finding of such extracolonic features in patients with non-FAP colorectal cancer is of considerable interest because of the central, and probably initiating, role of the gene for FAP (APC) in colorectal tumorigenesis. Constitutional and heterozygous mutation of the APC gene is responsible for the FAP syndrome (Groden et al., 1991; Nishishio et al., 1991;Nagase and Nakamura, 1993), while a high proportion of non-FAP colorectal adenomas and cancers have somatic APC mutations (Powell et al., 1992; Ichii et al., 1993; Nagasse and Nakamura, 1993). Inactivating APC mutations have also been noted in dysplastic aberrant crypt foci Smith et al., 1984), which are believed to be the very earliest histological manifestation of colorectal neoplasia.The available data suggest that the extracolonic manifestations of FAP, which we term attenuated extracholonic manifestations (AEMs), occur particularly in colorectal cancer patients with a family history of the disease (Sondergaard et al., 1985b; Houlston et al., 1992; Hunt et al., 1994). Thus we wished to determine whether there was any link with hereditary non-polyposis colorectal cancer (HNPCC), which is responsible for 2-5% of all colorectal cancer cases. HNPCC gene carriers develop few colorectal adenomas but are at high risk of colorectal cancer, particularly of the right colon, as well as other cancers Jass et al., 1994). Causative germline mutations in the DNA mismatch repair (MMR) genes hMSH2, hMLHI, hPMSJ and hPMS2 (Liu et al., 1996) have been identified in HNPCC families. Such mutations result in defective MMR (Parsons et al., 1993;Umar et al., 1994), manifest as instability of repetitive DNA in tumours (Ionov et al., 1993;Aaltonen et al., 1993;Thibodeau et al., 1993;Lothe et al., 1993;Aaltonen et al., 1994;Bhattacharyya et al., 1994;Liu et al., 1995a) (Traboulsi et al., 1987; Chapman et al., 1988;Berk et al., 1988; Giardello et al., 1991; Hodgson et al., 1994;Wallis et al., 1994). Because of the variety of CHRPE lesions, we devised a scoring system derived from the relative importance ascribed to each feature in previous FAP studies. Pigmented haloed lesions and lesions > 1 disc diameter scored 5: small lesions scored 1 and the total score for bilateral lesions was doubted.Posteroanterior, occlusal and pantomographic radiographic views of the mand...

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Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients

Cited by 277 publications

References 40 publications

APC mutation and phenotypic spectrum of Singapore familial adenomatous polyposis patients

APC mutation and phenotypic spectrum of Singapore familial adenomatous polyposis patients

Three submicroscopic deletions at the APC locus and their rapid detection by quantitative-PCR analysis

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer

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