The Fragile X CGG Repeat Shows a Marked Level of Instability in Hereditary Non-Polyposis Colorectal Cancer Patients

Fulchignoni-Lataud, Marie Claude; Olchwang, S.; Serre, J.L.

doi:10.1159/000484739

Cited by 6 publications

(3 citation statements)

References 18 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Martin et al [2000] found that male MSH2 gene mutation carriers have higher rates of aneuploidy and mutations in their sperm than noncarriers. In addition, a study of MLH1 mutation carriers found increased variability and lengthening of the fragile-X repeat of carriers compared to controls, suggesting MMR deficiency during gametogenesis could increase the likelihood of transition from normal to a premutation range of repeats in genes with dynamic mutations [Fulchignoni-Lataud et al, 1997]. …”

Section: Introductionmentioning

confidence: 99%

Dependence of colorectal cancer risk on the parent-of-origin of mutations in DNA mismatch repair genes

et al. 2011

View full text Add to dashboard Cite

Genetic diseases associated with dynamic mutations in microsatellite DNA often display parent-of-origin effects (POEs) in which the risk of disease depends on the sex of the parent from whom the disease allele was inherited. Carriers of germline mutations in mismatch repair (MMR) genes have high risks of colorectal carcinoma (CRC). We investigated whether these risks depend on the parent-of-origin of the mutation. We studied 422 subjects, including 89 MMR gene mutation carriers, from 17 population-based families who were each recruited via a CRC case diagnosed before age 45 years and found to carry a MMR gene mutation. The POE hazard ratio (HRPOE), defined to be the CRC incidence for carriers with maternally derived mutations divided by the corresponding paternal incidence, was estimated using a novel application of modified segregation analysis. HRPOE (95% confidence interval) was estimated to be 3.2 (1.1–9.8) for males (P=0.03) and 0.8 (0.2–2.8) for females (P=0.5) and the corresponding cumulative risks to age 80 years were 88% (54%–100%) for male carriers with maternally derived mutations and 38–48% for all other carriers. If confirmed by larger studies, these results will have important implications for the etiology of CRC and for the clinical management of MMR gene mutation carriers.

show abstract

Section: Introductionmentioning

confidence: 99%

Dependence of colorectal cancer risk on the parent-of-origin of mutations in DNA mismatch repair genes

et al. 2011

View full text Add to dashboard Cite

show abstract

“…One consequence of MMR deficiency is somatic instability of microsatellite repeat sequences. Fulchignoni-Lataud and colleagues 201 found some indication of increased somatic instability at the FMR1 CGG repeat in HNPCC patients compared with a control group. Although this study only analysed somatic instability, there is evidence that instability at the FMR1 locus is well correlated in both somatic and germinal cells.…”

Section: Mismatch Repair Defectsmentioning

confidence: 96%

“…200 One such mechanism could be defects in the DNA mismatch repair (MMR) genes and this has been explored in people known to have such a genetic mutation. 201 The cancer predisposition in most individuals with hereditary non-polyposis colorectal cancer (HNPCC) is attributable to mutations in any one of the five MMR genes. One consequence of MMR deficiency is somatic instability of microsatellite repeat sequences.…”

Section: Mismatch Repair Defectsmentioning

confidence: 99%

An assessment of screening strategies for fragile X syndrome in the UK

Pembrey¹,

Barnicoat²,

Carmichael³

et al. 2001

Health Technol Assess

View full text Add to dashboard Cite

Health Technology Assessment is indexed in Index Medicus/MEDLINE and Excerpta Medica/ EMBASE. Copies of the Executive Summaries are available from the NCCHTA website (see opposite). NHS R&D HTA Programme T he NHS R&D Health Technology Assessment (HTA) Programme was set up in 1993 to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and provide care in the NHS. Initially, six HTA panels (pharmaceuticals, acute sector, primary and community care, diagnostics and imaging, population screening, methodology) helped to set the research priorities for the HTA Programme. However, during the past few years there have been a number of changes in and around NHS R&D, such as the establishment of the National Institute for Clinical Excellence (NICE) and the creation of three new research programmes: Service Delivery and Organisation (SDO); New and Emerging Applications of Technology (NEAT); and the Methodology Programme. This has meant that the HTA panels can now focus more explicitly on health technologies ('health technologies' are broadly defined to include all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long term care) rather than settings of care. Therefore the panel structure has been redefined and replaced by three new panels: Pharmaceuticals; Therapeutic Procedures (including devices and operations); and Diagnostic Technologies and Screening. The HTA Programme will continue to commission both primary and secondary research. The HTA Commissioning Board, supported by the National Coordinating Centre for Health Technology Assessment (NCCHTA), will consider and advise the Programme Director on the best research projects to pursue in order to address the research priorities identified by the three HTA panels. The research reported in this monograph was funded as project number 93/34/04. The views expressed in this publication are those of the authors and not necessarily those of the HTA Programme or the Department of Health. The editors wish to emphasise that funding and publication of this research by the NHS should not be taken as implicit support for the recommendations for policy contained herein. In particular, policy options in the area of screening will be considered by the National Screening Committee. This Committee, chaired by the Chief Medical Officer, will take into account the views expressed here, further available evidence and other relevant considerations. Criteria for inclusion in the HTA monograph series Reports are published in the HTA monograph series if (1) they have resulted from work commissioned for the HTA Programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors. Reviews in Health Technology Assessment are termed 'systematic' when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication ...

show abstract

Haplotypic determinants of instability in the FRAX region: Concatenated mutation or founder effect?

Ennis

Morton

2001

Hum. Mutat.

View full text Add to dashboard Cite

The fragile X triplet repeat expansion at Xq27.3 has been shown to be associated with mutation or instability 600 kb distal at the FMR2 repeat locus. Concatenated mutation, whereby a mutation at one locus somehow interacts with mutation, recombination, deletion, or transposition at another locus, is a possible explanation. In this study we examine evidence from a sample of over 7,000 independent haplotypes from the FRAX region. We adopt the use of cladistic groups to more thoroughly define the properties of these haplotypes, and in doing so isolate one group of haplotypes which may be predisposed to the phenomenon of concatenated mutation. Distinguishing concatenated mutation from founder effects is difficult within a single population. We present our evidence for and against concatenated mutation, and in the process describe a previously undefined mutation at FRAXE.

show abstract

The Fragile X CGG Repeat Shows a Marked Level of Instability in Hereditary Non-Polyposis Colorectal Cancer Patients

Cited by 6 publications

References 18 publications

Dependence of colorectal cancer risk on the parent-of-origin of mutations in DNA mismatch repair genes

Dependence of colorectal cancer risk on the parent-of-origin of mutations in DNA mismatch repair genes

An assessment of screening strategies for fragile X syndrome in the UK

Haplotypic determinants of instability in the FRAX region: Concatenated mutation or founder effect?

Contact Info

Product

Resources

About