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.