2006
DOI: 10.1007/s10689-006-0014-8
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The phenotypic expression of three MSH2 mutations in large Newfoundland families with Lynch syndrome

Abstract: To compare the phenotypic expression of three different MSH2 mutations causing Lynch syndrome, 290 family members at 50% risk of inheriting a mutation were studied. Two truncating mutations of the MSH2 gene have been identified in Newfoundland: an exon 8 deletion in five families (N=74 carriers) and an exon 4-16 deletion in one family (N=65 carriers). The third mutation was an intron 5 splice site mutation resulting in deletion of exon 5 in RNA and occurred in 12 families (N=151 carriers). Age to onset of firs… Show more

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Cited by 33 publications
(29 citation statements)
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“…Interestingly, in humans, in-frame deletion of exon 5 of MSH2 is the most common mutation in HNPCC families, accounting for 11% of all known pathogenic MSH2 mutations (36). It results in an incomplete protein (37), and carriers have a high risk of developing cancers (38), which generally are microsatellite instable (39). This suggests that the splice site mutation of msh2 in zebrafish results in loss of function of the gene and provides a translational animal model for MSH2-driven disease in humans.…”
Section: Resultsmentioning
confidence: 99%
“…Interestingly, in humans, in-frame deletion of exon 5 of MSH2 is the most common mutation in HNPCC families, accounting for 11% of all known pathogenic MSH2 mutations (36). It results in an incomplete protein (37), and carriers have a high risk of developing cancers (38), which generally are microsatellite instable (39). This suggests that the splice site mutation of msh2 in zebrafish results in loss of function of the gene and provides a translational animal model for MSH2-driven disease in humans.…”
Section: Resultsmentioning
confidence: 99%
“…D2S123 and D2S119 surround hMSH2 and hMLH1, whereas D3S1611 is located within hMLH1. [28][29] Length changes in these microsatellites might serve as expressionregulating factors, affecting the activity of these genes.…”
Section: Discussionmentioning
confidence: 99%
“…6 Similarly, specific alleles in cancer predisposition genes may be more common in certain ethnic groups, such as 999del5 in BRCA2 (breast cancer 2, early onset) among Icelandic families with breast cancer 7 or founder MSH2 (MutS protein homolog 2) mutations in Lynch syndrome in Newfoundland and Labrador. 8 Awareness of such variation in distribution of disease has allowed an important preventative health strategy: using ethnic background to identify people who should be offered screening for conditions such as sickle cell anemia, thalassemias and Tay-Sachs disease. Taking a detailed three-generation family history 9 may provide useful clues as to whether a condition is familial and what the reasons for that might be -genes, shared environment or interactions between them.…”
Section: Key Pointsmentioning
confidence: 99%