An intrachromosomal insertion causing 5q22 deletion and familial adenomatous polyposis coli in two generations.

Cross, I; Delhanty, Jda; Chapman, Peter; Bowles, L.; Griffin, D.K.; Wolstenholme, John; Bradburn, Mike; Brown, Jennifer; Wood, C. B.; Gunn, Alexander D. G.

doi:10.1136/jmg.29.3.175

Cited by 41 publications

(31 citation statements)

References 12 publications

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“…Only 37 cases with interstitial deletions of the middle portion of the long arm of chromosome 5 have been reported (Garcia-Minaur et al 2005). Most reported cases of 5q deletions are de novo aberrations, except for three cases with an inherited deletion (Hockey et al 1989;Cross et al 1992;Hastings et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and molecular characterisation of a de novo 5q deletion that includes the APC gene

et al. 2005

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We report on a 12-year-old female patient with mild dysmorphic signs, including bilateral epicanthal folds, low-set dysplastic ears, a short nose with anteverted nostrils, conically shaped fingers, generalised increase of subcutaneous fat, multiple fine venous teleangiectasia on her back, mild pectus carinatum, and a general muscular hypotonia. Cytogenetic analysis and fluorescence in situ hybridisation (FISH) studies using region-specific BAC and YAC clones indicated a de novo interstitial deletion of the long arm of chromosome 5, resulting in monosomy 5q21.1-q23.1. Molecular analysis of polymorphic markers helped to narrow down the breakpoints and demonstrated that the derivative chromosome 5 is of paternal origin. By using the same panel of polymorphic markers, a reinvestigation of a similar, already published, 5q deletion case [Raedle et al. (2001) Am J Gastroenterol 96:3016-3020] was performed, allowing a more detailed genotype-phenotype correlation. Phenotypic classification was also carried out. Several known genes, including APC and MCC, were found to map to the common deleted genomic segment. Genetic counselling based on the molecular analysis data was performed for the index family.

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Section: Discussionmentioning

confidence: 99%

Phenotypic and molecular characterisation of a de novo 5q deletion that includes the APC gene

et al. 2005

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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%

“…[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. An intragenic APC deletion of 300 bp has recently been described in an Italian polyposis patient.…”

Section: Introductionmentioning

confidence: 99%

“…[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. 14 Here we describe three FAP families with 5q submicroscopic deletions encompassing the APC and DP1 genes.…”

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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“…(iii) A somatic cell hybrid, SD/Ts-1, derived from patient P.S. (26), containing a single copy of a chromosome 5 with a deletion around region q22-q23, known to include both YACs (data not shown) was also included to assess each cosmid (12).…”

Section: Resultsmentioning

confidence: 99%

Yeast artificial chromosomes for the molecular analysis of the familial polyposis APC gene region.

Ward¹,

Cottrell²,

Howe³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Two yeast artificial chromosomes (YACs) spanning a total distance of 1.1 megabase pairs of DNA around the MCC (for mutated in colorectal carcinoma) and APC (for adenomatous polyposis coli) genes at 5q21 have been isolated and characterized. Starting from the MCC gene, a strategy was undertaken to identify constitutional submicroscopic deletions in familial adenomatous polyposis patients that might considerably narrow down the position of the APC gene. To this end, YACs identified by the MCC gene were screened across a chromosome 5-specific cosmid library to provide a source of DNA probes for genomic sanning. The cosmids isolated from these experiments were used to screen a panel of somatic cell hybrids containing chromosome 5 segregated from patients suspected to carry putative interstitial deletions. This screening approach led to the confirmation of a small heterozygous deletion in a polyposis patient that overlaps one of the two isolated YACs. This YAC has been shown to contain the entire APC gene, in addition to a significant portion of DNA flanking the 5' end of the gene, and should therefore prove a valuable resource for functional studies by transfer to colorectal tumorderived cell lines.Familial adenomatous polyposis (FAP) is an autosomal dominant predisposition to colorectal cancer, affecting about 1 in 5000 to 1 in 10,000 individuals in all populations studied (1).The corresponding gene, designated APC [for adenomatous polyposis coli (2)], was mapped to 5q21-q22 by linkage analysis (3, 4) following a cytogenetic report of a male patient with polyposis and an interstitial deletion on Sq (5). The high incidence of allele loss at 5q21-q22 in carcinomas of sporadic patients (6-9) suggests that APC mutations are common in sporadic colorectal adenocarcinomas.To clone the APC gene, our initial studies used two deletions similar to that originally identified by Herrera et al.(5) to localize probes to a region around the APC gene (10). Subsequently, landmark clones were derived by chromosomal microdissection and microcloning around 5q21-q22 (11,12). Clones that were localized within the two APC-related interstitial deletions were then used to isolate yeast artificial chromosomes (YACs) covering about 4 megabases (ref. 12; G.M.H. and J.R.T.J.W., unpublished results) in order to narrow the search for the APC gene among potential candidates.During this investigation, however, a candidate gene, MCC (for mutated in colorectal carcinoma), was identified by using a randomly isolated cosmid, L5.71, exhibiting a high frequency of allele loss (13) and which also identified a heterozygous 260-kilobase (kb) deletion in one polyposis family (14). After the discovery of MCC, Kinzler et al. (15) and Groden et al. (16) isolated the APC gene itself. In this paper we describe our approach to identifying the APC gene, which has led to the isolation of two overlapping YACs containing the MCC gene, one of which also includes the complete APC gene. MATERIALS AND METHODS YACMethods. The YAC library used in these studies (17)...

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An intrachromosomal insertion causing 5q22 deletion and familial adenomatous polyposis coli in two generations.

Cited by 41 publications

References 12 publications

Phenotypic and molecular characterisation of a de novo 5q deletion that includes the APC gene

Phenotypic and molecular characterisation of a de novo 5q deletion that includes the APC gene

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

Yeast artificial chromosomes for the molecular analysis of the familial polyposis APC gene region.

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