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A frame-shift mutat...
A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome
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Clendenning, M (author)
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Senter, L (author)
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Hampel, H (author)
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- Lagerstedt Robinson, K (author)
- Karolinska Institutet
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Sun, S (author)
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Buchanan, D (author)
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Walsh, M D (author)
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- Nilbert, Mef (author)
- Lund 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
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Green, J (author)
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Potter, J (author)
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- Lindblom, A (author)
- Karolinska Institutet
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de la Chapelle, A (author)
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(creator_code:org_t)
- 2008-01-30
- 2008
- English.
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In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 45:6, s. 340-345
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http://dx.doi.org/10...
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https://europepmc.or...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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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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show more...
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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Journal of Medic ...
- By the university
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Lund University
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Karolinska Institutet