title: A novel germline MLH1 mutation causing Lynch Syndrome in patients from the Republic of Macedonia.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Pharmacy, Ss. Cyril and Methodius University, Vodnjanska 17, Skopje, Republic of Macedonia.
authors.forename: Marija
authors.initials: M
authors.lastname: Hiljadnikova-Bajro
authors.forename: Toni
authors.initials: T
authors.lastname: Josifovski
authors.forename: Milco
authors.initials: M
authors.lastname: Panovski
authors.forename: Aleksandar J
authors.initials: AJ
authors.lastname: Dimovski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011446:Prospective Studies; D018843:Republic of North Macedonia; D017422:Sequence Analysis, DNA
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein