Founder mutation in Lynch syndrome

• Published in: Medicina (Buenos Aires) Vol. 76; no. 3; pp. 180 - 182
• Main Authors: Cajal, Andrea R, Piñero, Tamara A, Verzura, Alicia, Santino, Juan Pablo, Solano, Angela R, Kalfayan, Pablo G, Ferro, Alejandra, Vaccaro, Carlos
• Format: Journal Article
• Language: Spanish
• Published: Argentina 2016
• Subjects: Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; DNA Repair - genetics; Female; Founder Effect; Humans; Lynch Syndrome II - genetics; Middle Aged; Mismatch Repair Endonuclease PMS2 - genetics; Mutation - genetics; MutL Protein Homolog 1 - genetics; Pedigree; MLH1 gene; Lynch syndrome; founder mutation
• ISSN: 0025-7680

Lynch syndrome is the most frequent syndrome in hereditary colorectal cancer, a family-specific deleterious mutations in genes encoding DNA reparation proteins: MLH1 (mutL homolog 1), MSH2, MSH6 (mutS homolog 2 y 6, respectively), PMS2 (PMS1 homolog 2, mismatch repair system component) y MUTYH (mutY DNA glycosylase). The c.2252_2253delAA, p.Lys751Serfs*3 mutation in MLH1 gene segregates with a haplotype reported in the northern region of Italy and whose origin was attributed to a founder effect. This mutation co-segregates with typical characteristics of Lynch syndrome, including early age at onset and multiple primary tumors in the same individual, a high frequency of pancreatic cancer, high microsatellite instability and lack of PMS2 expression. This report describes a mutation in an Argentinian patient with endometrioid adenocarcinoma of uterus. Her first-degree relatives had a history of colon cancer diagnosed before 50 years, fulfilling the Amsterdam Criteria I and Lynch syndrome II. The high pathogenicity associated to this mutation makes necessary the study of all members from families with hereditary cancer, allowing pre-symptomatic genetic diagnosis, early assessment and the instauration of preventive treatments.