A novel germline MLH1 mutation causing Lynch Syndrome in patients from the Republic of Macedonia

AIM: To implement molecular analysis in the clinical diagnosis and management of Lynch syndrome (LS). METHODS: We analyzed the mutations in MLH1 and MSH2 in the selected LS families from the Republic of Macedonia. RESULTS: We performed the very first genetic identification of LS families and characterized a novel mutation. The novel nonsense germline point mutation c.392C>G in the codon 131 of MLH1(S131X) was identified as the underlying genetic cause of LS in three families. The haplotype analysis suggested a founder effect of this mutation in our population. CONCLUSION: We expect to detect the mutation in other LS patients from the region, and recommend cost-effective screening for this mutation by restriction fragment length polymorphism-polymerase chain reaction or DNA sequencing of MLH1 Exon5 prior to full genetic testing in all LS suspects of Macedonian ancestry.