Founder mutations in specific populations are common in several Mendelian disorders. They are shared by apparently unrelated families that inherited them from a common ancestor that existed hundreds to thousands of years ago. They have been proven to impact in molecular diagnostics strategies in specific populations, where they can be assessed as the first screening step and, if positive, avoid further expensive gene scanning. In Lynch syndrome (LS), a dominantly inherited colorectal cancer disease, more than 50 founder pathogenic mutations have been described so far in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2). We here provide a comprehensive summary of the founder mutations found in the MMR genes and an overview of their main characteristics. At a time when high-throughput strategies are being introduced in the molecular diagnostics of cancer, genetic testing for founder mutations can complement next generation sequencing (NGS) technologies to most efficiently identify MMR gene mutations in any given population. Additionally, special attention is paid to MMR founder mutations with interesting anthropological significance.
Keywords: HNPCC; Lynch syndrome; MLH1; MMR; MSH2; MSH6; Muir-Torre syndrome; PMS2; founder mutation; genetic anticipation phenomenon.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.