[Founder mutation in Lynch syndrome].
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.
Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Instituto Universitario Hospital Italiano, Argentina. E-mail: andrea.cajal@hiba.org.ar.
Andrea R
AR
Cajal
Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Instituto Universitario Hospital Italiano, Argentina.
Tamara A
TA
Piñero
Programa de Cáncer Hereditario (ProCanHe), Hospital Italiano de Buenos Aires, Argentina.
Alicia
A
Verzura
Programa de Cáncer Hereditario (ProCanHe), Hospital Italiano de Buenos Aires, Argentina.
Juan Pablo
JP
Santino
Genotipificación y Cáncer Hereditario, Departamento de Análisis Clínicos, CEMIC, Argentina.
Angela R
AR
Solano
rograma de Cáncer Hereditario (ProCanHe), Hospital Italiano de Buenos Aires, Argentina.
Pablo G
PG
Kalfayan
Programa de Cáncer Hereditario (ProCanHe), Hospital Italiano de Buenos Aires, Argentina.
Alejandra
A
Ferro
Programa de Cáncer Hereditario (ProCanHe), Hospital Italiano de Buenos Aires, Argentina.
Carlos
C
Vaccaro
D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D005260:Female; D018703:Founder Effect; D006801:Humans; D055847:Lynch Syndrome II / Q000235:genetics; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics*; D000070957:MutL Protein Homolog 1 / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1
Lynch syndrome; MLH1 gene; founder mutation