[Detection of a founder mutation in an Argentine family with hereditary non polyposis colorectal cancer].
Hereditary non polyposis colorectal cancer (HNPCC) has been related to mutations in the DNA mismatch repair genes (MLH1, MSH2 y MSH6). Mutation detection analysis requires the complete sequencing of these genes, given the high frequency of family-specific alterations. A point mutation (2269-2270insT) in the last codon of the MLH1 gene has been detected in families from a northern region of Italy (Reggio Emilia).Given that this alteration was registered only in people from this region, it has been considered a founder mutation. In this work, we present an Argentine HNPCC family whose ancestors were natives from the Reggio Emilia, Italy, and who were carriers for this mutation. In order to detect the genetic alteration, a PCR was developed followed by a restriction enzyme incubation assay. The mutation was detected in 3 family members, two of them without clinical symptoms. The PCR/restriction enzyme methodology has been sensitive and specific for the detection of this mutation. It has allowed the performance of a pre-symptomatic genetic diagnosis in the Argentine HNPCC family, avoiding sending samples abroad. It is worth mentioning that pre-symptomatic diagnosis of hereditary cancers allows enhanced surveillance and support for the affected families when it is performed by a multidisciplinary group.
Laboratorio de Biología Celular y Molecular, Instituto de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, CCT-Mendoza-CONICET.
Laura
L
Gómez
José
J
Adi
Jorge
J
Ibarra
María
M
Roqué
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D017422:Sequence Analysis, DNA
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1
Mutación fundadora en una familia argentina con cáncer colorrectal hereditario.