Recurrent and founder mutations in the PMS2 gene. (4th June 2012)

• Record Type: Journal Article
• Authors: Tomsic, J; Senter, L; Liyanarachchi, S; Clendenning, M; Vaughn, C P; Jenkins, M A; Hopper, J L; Young, J; Samowitz, W; de la, A
• Is Part Of: Clinical genetics. Volume 83:Number 3(2013:Mar.)
• Page Start: 238
• Page End: 243
• Publication Date: 2012-06-04
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/j.1399-0004.2012.01898.x
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Germline mutations in <italic>PMS2</italic> are associated with Lynch syndrome (LS), the most common known cause of hereditary colorectal cancer. Mutation detection in <italic>PMS2</italic> has been difficult due to the presence of several pseudogenes, but a custom‐designed long‐range PCR strategy now allows adequate mutation detection. Many mutations are unique. However, some mutations are observed repeatedly across individuals not known to be related due to the mutation being either recurrent, arising multiple times <italic>de novo</italic> at hot spots for mutations, or of founder origin, having occurred once in an ancestor. Previously, we observed 36 distinct mutations in a sample of 61 independently ascertained Caucasian probands of mixed European background with <italic>PMS2</italic> mutations. Eleven of these mutations were detected in more than one individual not known to be related and of these, six were detected more than twice. These six mutations accounted for 31 (51%) ostensibly unrelated probands. Here, we performed genotyping and haplotype analysis in four mutations observed in multiple probands and found two (c.137G>T and exon 10 deletion) to be founder mutations and one (c.903G>T) a probable founder. One (c.1A>G) could not be evaluated for founder mutation status. We discuss possible explanations for the frequent occurrence of founder mutations in <italic>PMS2</italic>.</p> </abstract>