Haplotype analysis suggest that the MLH1 c.2059C   & gt;  T mutation is a Swedish founder mutation

AbstractLynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genesMLH1, MSH2, MSH6 orPMS2, with the vast majority detected inMLH1 andMSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also acting as founders in other ethnic groups. Testing for founder mutations can facilitate molecular diagnosis of Lynch Syndrome more efficiently and more cost effective than screening for all possible mutations. Here we report a study of the missense mutationMLH1 c.2059C  >  T (p.Arg687Trp), a potential founder mutation identified in eight Swedish families and one Finnish family with Swedish ancestors. Haplotype analysis confirmed that the Finnish and Swedish families shared a haplotype of between 0.9 and 2.8 Mb. WhileMLH1 c.2059C  >  T exists worldwide, the Swedish haplotype was not found among mutation carriers from Germany or France, which indicates a common founder in the Swedish population. The geographic distribution ofMLH1 c.2059C  >  T in Sweden suggests a single, ancient mutational event in the northern part of Sweden.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research