Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Severe upper gastrointestinal polyposis associated with sparse colonic polyposis in a familial adenomatous polyposis family with an APC mutation at codon 1520.

ABSTRACT: BACKGROUND: Familial adenomatous polyposis usually results in colonic polyposis with hundreds to thousands of polyps, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and variable extracolonic features. Recent reports indicate that patients with distal mutations between codons 1445 and 1578 do not express CHRPE and have a high incidence of desmoid tumours. PATIENTS: The family studied has an unusual phenotype of sparse colonic polyposis but profuse upper gastrointestinal polyposis. Affected subjects do not have CHRPE. METHODS: The protein truncation test followed by sequencing identified a 2 base pair deletion at codon 1520 in the APC gene. This results in a frameshift creating a stop codon 13 codons downstream. RESULTS: This family demonstrates that sparse colonic polyposis but severe upper tract polyposis may be associated with mutations between codons 1445 and 1578. CONCLUSIONS: Study of duodenal and colonic polyps in further cases with mutations in this region is warranted. Such mutations may preferentially cause duodenal adenomas and desmoid tumours as somatic mutations in these tumours also occur in this region, unlike colorectal tumours where somatic mutations occur more proximally. This study emphasises the importance of screening the upper gastrointestinal tract even when the colonic disease is mild.

SUBMITTER: Leggett BA

PROVIDER: S-EPMC1891546 | biostudies-other | 1997 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype.

Project description:BACKGROUND:Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli (APC) gene in approximately 80% of patients. The APC protein comprises several regions and domains for interaction with other proteins, and specific clinical manifestations are associated with the mutation assignment to one of these regions or domains. AIMS:The phenotype in patients without an identified causative APC mutation was compared with the phenotype in patients with a known APC mutation and with the phenotypes characteristic of patients with mutations in specific APC regions and domains. PATIENTS:Data on 121 FAP probands and 149 call up patients from 70 different families were extracted from the Danish Polyposis register. METHODS:Differences in 16 clinical manifestations were analysed according to the patient's mutational status. Two sided independent t sample test, two sided chi(2) test, and odds ratios were calculated. RESULTS:Patients without identified APC mutations had a unique and severe phenotype, which was roughly described as: young age at diagnosis and subsequent death in spite of development of few colorectal adenomas; low risk of involvement of the upper gastrointestinal tract, as reflected by a low mean Spigelman stage, and a low risk of fundic gland polyposis. Finally, they had significantly fewer affected family members, although they do not themselves more often represent an isolated case. CONCLUSIONS:The severe phenotype should be considered when counselling FAP families in which attenuated FAP is excluded and in which a causative APC mutation has not been identified.

| S-EPMC1774914 | biostudies-literature

Pathogenic APC Variants in Latvian Familial Adenomatous Polyposis Patients.

Project description:Background and objectives: Familial adenomatous polyposis is one of the APC-associated polyposis conditions described as genetically predetermined colorectal polyposis syndrome with a variety of symptoms. The purpose of this study was to determine sequence variants of the APC gene in patients with familial adenomatous polyposis (FAP) phenotype and positive or negative family history. Materials and Methods: Eight families with defined criteria of adenomatous polyposis underwent molecular genetic testing. Coding regions and flanking intron regions of the APC gene were analyzed by Sanger sequencing. Results: Eight allelic variants of the APC gene coding sequence were detected. All allelic variants of the APC gene were predicted to be pathogenic based on criteria according to the "Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology" (2015), four of them c.1586_1587insAT, c.2336delT, c.3066_3067insGA, and c.4303_4304insC, were considered novel. Conclusions: The timely molecular genetic analysis of APC germline variants and standardized interpretation of the pathogenicity of novel allelic variants has a high impact on choice for treatment, cancer prevention, and family genetic counseling.

| S-EPMC6843383 | biostudies-literature

APC gene mutations in Chinese familial adenomatous polyposis patients.

Project description:AimTo study the characteristics of APC (adenomatous polyposis coli) gene germline mutation in Chinese patients with familial adenomatous polyposis (FAP).MethodsAPC gene from 14 FAP families was amplified by polymerase chain reaction (PCR) and underwent direct sequencing to determine the micromutation type. For the samples without micromutation, the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification (MLPA).ResultsThere were gene micromutations in 9 families with a micromutation detection rate of 64.3% (9/14), including 6 frameshift mutations (66.7%), 1 nonsense mutation (11.1%) and 2 splicing mutations (22.2%). Large fragment deletions were detected by MLPA in 2 families. The total mutation detection rate of micromutations and large fragment deletions was 78.6% (11/14).ConclusionThe detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.

| S-EPMC2846260 | biostudies-literature

APC transcription studies and molecular diagnosis of familial adenomatous polyposis.

Project description:Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of colorectal adenomas and results from inherited or somatic mosaic variants in the APC gene. Index patients with suspected FAP are usually investigated by APC coding region sequence and dosage analysis in a clinical diagnostic setting. The identification of an APC variant which is predicted to alter protein function enables predictive genetic testing to guide the management of family members. This report describes a 4-generation family with a phenotype consistent with FAP, but in which an APC variant had not been identified, despite testing. To explore this further, quantitative PCR (qPCR) was employed to assess APC transcription, demonstrating reduced levels of APC RNA. Next generation sequencing (NGS) identified the APC 5'UTR/ Exon 1 variant, c.-190 G>A, that had been reported previously in an another FAP family with APC allelic imbalance. Quantitative RNA studies and DNA sequencing of the APC promoters/ Exon 1 may be useful diagnostically for patients with suspected FAP when coding region variants cannot be identified.

| S-EPMC6906400 | biostudies-literature

Wild-type APC Influences the Severity of Familial Adenomatous Polyposis.

Project description: Not available

| S-EPMC8777002 | biostudies-literature

A novel large germ line deletion in adenomatous polyposis coli (APC) gene associated with familial adenomatous polyposis.

Project description:BACKGROUND:Familial adenomatous polyposis (FAP) is a familial colorectal cancer predisposition syndrome characterized by the development of numerous colorectal polyps, which is inherited in an autosomal dominant manner. FAP is caused by germ line mutations in adenomatous polyposis coli (APC) gene. Here, we described the identification of a causative APC gene deletion associated with FAP in an Iranian family. METHODS:Diagnosis of FAP was based on clinical findings, family history, and medical records (colonoscopy and histopathological data) after the patients were referred to Reza Radiotherapy and Oncology Center, Iran, for colonoscopy. Blood samples were collected, and genomic DNA was extracted. APC mutation screening was conducted by target next-generation sequencing and quantitative real-time PCR. RESULTS:A novel heterozygous large deletion mutation, c.(135+1_136-1)_(*2113+1_*2114-1) spanning exon 3 to 16 [EX3_16 DEL] of APC gene (GenBank Accession# MG712911), was detected in a proband and all her affected relatives in five generations, which was absent in unaffected family members and normal controls. CONCLUSIONS:This novel deletion is the first report, describing the largest deletion of APC gene. Our novel finding contributes to a more comprehensive database of germ line mutations of APC gene that could be used in medical practice for the molecular diagnosis, risk assessment susceptibility of the disease for the FAP patients.

| S-EPMC6305644 | biostudies-literature

Upper Gastrointestinal Screening of Polyp Load in Children With Familial Adenomatous Polyposis: Is It Required?

Project description:Objectives and studyPatients with familial adenomatous polyposis (FAP) have a propensity to form not only large bowel polyps but also upper gastrointestinal (GI) polyps with malignant potential. International guidance suggests that upper GI screening need not begin until patients are at least into their twenties. It is our experience that patients develop upper GI polyps long before this point which have the potential for malignant change.MethodsA prospective record of all upper GI endoscopies in children (aged 9 to 17) with FAP was kept across a 12-year period by 1 surgeon in our center. For each scope performed, we recorded the location, histology, and treatment of upper GI polyps.ResultsTwent-eight patients aged 9 to 17 underwent a total of 48 esophagogastroduodenoscopies across a 12-year period. Thirty-eight esophagogastroduodenoscopies (79%) identified at least 1 gastric or duodenal polyp in 22 (79%) patients; 10 (36%) patients had gastric adenomas. Eight (29%) patients showed very high numbers of polyps. All 21 patients who had duodenal polyps had adenomas. None had yet developed malignancy, but 1 patient required extensive polyp excision and one is awaiting endoscopic mucosal resection.ConclusionOur results demonstrate that young people with FAP are at the risk of developing upper GI polyps long before current guidance suggests screening the upper GI tract. We advocate for screening of the upper GI tract to start along with colonoscopy and happen at the same sitting for pediatric and young adult patients with FAP.

| S-EPMC10754608 | biostudies-literature

Attenuated familial adenomatous polyposis with desmoids caused by an APC mutation.

Project description:We present here a case of attenuated familial adenomatous polyposis (AFAP) with a family history of desmoids and thyroid tumors. This patient had no colonic polyps but did have multiple desmoids. Genetic analysis identified a 4-bp deletion in codon 2644 (c.7932_7935delTTAT: p.Tyr2645LysfsX14) of the adenomatous polyposis coli (APC) gene. In cases with limited numbers of colonic polyps and desmoids, AFAP may be caused by a mutation in the 3' region of APC.

| S-EPMC4785566 | biostudies-literature

TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis.

Project description:Truncating mutations in the tumor suppressor gene adenomatous polyposis coli (APC) are the initiating step in the vast majority of sporadic colorectal cancers, and they underlie familial adenomatous polyposis (FAP) syndromes. Modeling of APC- driven tumor formation in the mouse has contributed substantially to our mechanistic understanding of the associated disease, but additional models are needed to explore therapeutic opportunities and overcome current limitations of mouse models. We report on a novel and penetrant genetic cancer model in Xenopus tropicalis, an aquatic tetrapod vertebrate with external development, diploid genome and short life cycle. Tadpoles and froglets derived from embryos injected with TAL effector nucleases targeting the apc gene rapidly developed intestinal hyperplasia and other neoplasms observed in FAP patients, including desmoid tumors and medulloblastomas. Bi-allelic apc mutations causing frame shifts were detected in the tumors, which displayed activation of the Wnt/β-catenin pathway and showed increased cellular proliferation. We further demonstrate that simultaneous double bi-allelic mutation of apc and a non-relevant gene is possible in the neoplasias, opening the door for identification and characterization of effector or modifier genes in tumors expressing truncated apc. Our results demonstrate the power of modeling human cancer in Xenopus tropicalis using mosaic TALEN-mediated bi-allelic gene disruption.

| S-EPMC4468341 | biostudies-literature

Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells.

Project description:Mutations in the gene Adenomatous Polyposis Coli or APC appear in most sporadic cases of colorectal cancer and it is the most frequent mutation causing hereditary Familial Adenomatous Polyposis. The detailed molecular mechanism by which APC mutations predispose to the development of colorectal cancer is not completely understood. This is in part due to the lack of accessibility to appropriate models that recapitulate the early events associated with APC mediated intestinal transformation. We have established a novel platform utilizing human induced Pluripotent Stem cells or iPSC from normal or FAP-specific APC mutant individuals and evaluated the effect of the mutation in the cells before and after differentiation into intestinal organoids. In order to minimize genetic background effects, we also established an isogenic platform using TALEN-mediated gene editing. Comparison of normal and APC mutant iPSC revealed a significant defect in cell identity and polarity due to the presence of APC in heterozygosity as well as chromosomal aberrations including abnormal anaphases and centrosome numbers. Importantly, upon specification into intestinal progeny, APC heterozygosity was responsible for a major change in the transcriptional identity of the cells with dysregulation of key signaling pathways, including metabolic reprogramming, abnormal lipid metabolism and intestinal-specific cadherin expression. In conclusion, we have developed a novel iPSC/intestinal model of APC mutagenesis and provide strong evidence that APC in heterozygosity imparts a clear phenotypic and molecular defect, affecting basic cellular functions and integrity, providing novel insights in the earlier events of APC-mediated tumorigenesis.

| S-EPMC6053155 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data