Novel germline APC gene mutation in a large familial adenomatous polyposis kindred displaying variable phenotypes.

Scott, Rodney J.; Luijt, Rob van der; Spycher, M; Mary, Jean-Luc; Müller, Andreas; Hoppeler, T; Häner, M; Müller, Hansjakob; Martinoli, S; Brazzola, Pierluigi

doi:10.1136/gut.36.5.731

Cited by 81 publications

(62 citation statements)

References 22 publications

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“…7,[38][39][40][41] Mutations at the 5' end of the APC gene are predicted to result in extremely short and presumably unstable truncated proteins. Consequently, these mutations might act as a null allele.…”

Section: Discussionmentioning

confidence: 99%

“…6 In addition to genotype and phenotype heterogeneity, patients with an identical mutation can exhibit phenotype variability, probably due to a modifying locus or environmental factors. [6][7][8] Due to the inherent difficulty in detecting gene deletions, interstitial 5q deletions that encompass the APC gene have been identified in very few FAP patients. [9][10][11][12][13][14][15][16] So far, large deletions account for about 2% of the identified germline mutations.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Indeed, researchers have identified correlations between specific mutational locations and the existence of extracolonic manifestations (Olschwang et al, 1993, Eccles et al, 1996, the number of colorectal adenomas (Scott et al, 1995), age at diagnosis of FAP and age at onset of colorectal cancer Friedl et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Mutation spectrum of the APC gene in 83 Korean FAP families

Kim

Kang

et al. 2005

Hum. Mutat.

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Familial adenomatous polyposis (FAP) is a clinically well-defined hereditary disease caused by germline mutations in the adenomatous 1438C>T, c.2232_2233dupCT, c.3426delT, c.3739_3769del31, c.3931_3935delATTGG, c.4332dupA, and c.4722_4725delACTA. Desmoid tumors were identified in 6 of the examined FAP patients, five of whom had APC germline mutations; these mutations involved codons 849, 864, 1309, 1444 and 1464, respectively (c.2547_2548delTA, c.2592_2593insCT, c.3927_3931delAAAGA, c.4332dupA and c.4391-4394delAGAG). Four of the included FAP patients had papillary thyroid cancers; all were female and had germline APC mutations (c.1863_1865delTTAincCT, c.2805C>A, c.3183_3187delACAAA and c.3927_3931delAAAGA).

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“…Although many studies have shown both inter-and intrafamilial phenotypic variations among patients carrying the identical mutation Paul et al 1993;Varesco et al 1993;Giardiello et al 1994;van der Luijt et al 1995;Scott et al 1995), some studies have indicated clear genotype-phenotype correlations between the location of the APC gene mutation and the characteristic manifestations of FAP. These include the number of polyps Spirio et al 1993;Gayther et al 1994;Scott et al Germline mutations of the APC gene in Korean familial adenomatous polyposis patients Friedl et al 1996), the age of onset and death Caspari et al 1994;Gayther et al 1994;Scott et al 1995;Friedl et al 1996), the presence of congenital hypertrophy of the retinal pigment epithelium (CHRPE) Caspari et al 1995), and the occurrence of desmoid tumors (Caspari et al 1995;Davies et al 1995;Scott et al 1995;Dobbie et al 1996;Eccles et al 1996). Thus, the evidence strongly suggests that there are different functional mutations within the APC gene with respect to the position of the mutation.…”

Section: Introductionmentioning

confidence: 99%

Germline mutations of the APC gene in Korean familial adenomatous polyposis patients

et al. 1999

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We extensively analyzed genomic DNA and messenger RNA (mRNA) from 62 unrelated Korean patients with familial adenomatous polyposis (FAP) for identification of germline adenomatous polyposis coli (APC) gene mutations. We adopted both single-strand conformation polymorphism (SSCP) analysis and a method of analysis involving the reverse transcription-polymerase chain reaction (RT-PCR) followed by a protein truncation test (PTT). DNA sequencing confirmed all alterations represented by aberrant bands. Germline mutations were identified in 38 patients (61%). Nineteen of the detected mutations were presumed to be novel, thus emphasizing the heterogeneity of the mutational spectrum in Korean FAP patients. In the initial 48 patients, SSCP analysis was followed by PTT for those patients for whom no detectable mutations were found by SSCP. Using this combined approach, we identified germline APC gene mutations in 29 of the 48 FAP patients (60%), including 6 patients in whom SSCP analysis failed to distinguish the mutant allele. In the 14 later patients, we identified truncating mutations in 9 patients (64%) using PTT only. Our results confirm that the mutation detection rate with PTT was superior to that with SSCP, and suggest that PTT would be a more practical screening method to detect germline mutations of the APC gene in FAP patients.

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Novel germline APC gene mutation in a large familial adenomatous polyposis kindred displaying variable phenotypes.

Abstract: The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli.

Cited by 81 publications

References 22 publications

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

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

Mutation spectrum of the APC gene in 83 Korean FAP families

Germline mutations of the APC gene in Korean familial adenomatous polyposis patients

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