Huntingtin gene CAG repeat size in patients with Lynch syndrome

Abstract

AbstractPatients with Lynch syndrome (LS) are prone to cancer due to heterozygous germline pathogenic variants in genes encoding DNA mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. LS cancer cells exhibit deficient DNA mismatch repair and microsatellite instability due somatic inactivation of the second copy of the affected gene. To study microsatellite characteristics in non-neoplastic cells in LS we determined CAG repeat size in the huntingtin gene (HTT) microsatellite in lymphocyte DNA from LS patients with germline pathogenic variants in MLH1 (n = 11), MSH2 (n = 9), MSH6 (n = 7) and non-LS controls (n=19). Mean repeat size in LS was 19,55 CAG (MLH1), 19,39 CAG (MSH2), 18.07 CAG (MSH6), respectively compared to 18,42 CAG in controls. Standard deviation for CAG repeat size in LS was 4,183 CAG (MLH1), 5,089 CAG (MSH2), 3,075 CAG (MSH6), respectively, compared to 3,342 CAG in controls. Peak CAG repeat size in LS was 32 CAG (MLH1), 32 CAG (MSH2), 24 CAG (MSH6), respectively compared to 27 CAG in controls. Collectively, our data indicate that HTT CAG repeat size tends to be larger and more variable in individuals with LS caused by pathogenic variants in MLH1 and MSH2.