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A frame-shift mutat...
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Clendenning, M
(författare)
A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome
- Artikel/kapitelEngelska2008
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:1e2b624c-2ee1-43ff-a0b6-dea2e4a8a974
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https://lup.lub.lu.se/record/1201190URI
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https://doi.org/10.1136/jmg.2007.056150DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:117151812URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Background: When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (<2% of all identified mutations), yet the immunohistochemical analysis of tumour samples indicates that approximately 5% of Lynch syndrome cases are caused by PMS2. This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences. Methods: Using a recently developed method for detecting PMS2 specific mutations, we have screened 99 patients who are likely candidates for PMS2 mutations based on immunohistochemical analysis. Results: We have identified a frequently occurring frame-shift mutation (c.736_741del 6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n = 61). These individuals all display the rare allele (population frequency <0.05) at a single nucleotide polymorphism (SNP) in exon 11, and have been shown to possess a short common haplotype, allowing us to calculate that the mutation arose around 1625 years ago (65 generations; 95% confidence interval 22 to 120). Conclusion: Ancestral analysis indicates that this mutation is enriched in individuals with British and Swedish ancestry. We estimate that there are >10 000 carriers of this mutation in the USA alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected in the probands' families, would suggest that this is a prevalent mutation with reduced penetrance.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Senter, L
(författare)
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Hampel, H
(författare)
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Lagerstedt Robinson, KKarolinska Institutet
(författare)
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Sun, S
(författare)
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Buchanan, D
(författare)
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Walsh, M D
(författare)
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Nilbert, MefLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-mni
(författare)
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Green, J
(författare)
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Potter, J
(författare)
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Lindblom, AKarolinska Institutet
(författare)
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de la Chapelle, A
(författare)
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Karolinska InstitutetBröstcancer-genetik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Medical Genetics: BMJ45:6, s. 340-3450022-25931468-6244
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Till lärosätets databas
- Av författaren/redakt...
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Clendenning, M
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Senter, L
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Hampel, H
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Lagerstedt Robin ...
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Sun, S
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Buchanan, D
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visa fler...
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Walsh, M D
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Nilbert, Mef
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Green, J
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Potter, J
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Lindblom, A
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de la Chapelle, ...
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visa färre...
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- Av lärosätet
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Lunds universitet
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Karolinska Institutet