title: Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome.
abstract: Background. Lynch Syndrome (LS) is characterized by germline mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC) and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC), and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del) and c.1852_1853delinsGC (p.K618A) in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs) in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel.
authors.affiliation: Instituto de Genética Humana, CUCS, Universidad de Guadalajara, Sierra Mojada 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico; Trayectoria de Genómica Alimentaria, Universidad de la Ciénega del Estado de Michoacán de Ocampo, Avenida Universidad 3000, Colonia Lomas de la Universidad, 59103 Sahuayo, MICH, Mexico.
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Moreno-Ortiz
authors.affiliation: Instituto de Genética Humana, CUCS, Universidad de Guadalajara, Sierra Mojada 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico.
authors.forename: María de la Luz
authors.initials: Mde L
authors.lastname: Ayala-Madrigal
authors.affiliation: Instituto de Genética Humana, CUCS, Universidad de Guadalajara, Sierra Mojada 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico; Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Salvador de Quevedo y Zubieta 750, 44340 Guadalajara, JAL, Mexico.
authors.forename: Jorge Román
authors.initials: JR
authors.lastname: Corona-Rivera
authors.affiliation: Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Salvador de Quevedo y Zubieta 750, 44340 Guadalajara, JAL, Mexico.
authors.forename: Manuel
authors.identifier: 0000-0002-3430-9685
authors.initials: M
authors.lastname: Centeno-Flores
authors.affiliation: Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Salvador de Quevedo y Zubieta 750, 44340 Guadalajara, JAL, Mexico.
authors.forename: Víctor
authors.initials: V
authors.lastname: Maciel-Gutiérrez
authors.affiliation: Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Salvador de Quevedo y Zubieta 750, 44340 Guadalajara, JAL, Mexico.
authors.forename: Ramón Antonio
authors.initials: RA
authors.lastname: Franco-Topete
authors.affiliation: Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara, Sierra Mojada 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Armendáriz-Borunda
authors.affiliation: GI Cancer Research Laboratory, Baylor University Medical Center, 3500 Gaston Avenue, Suite 250 Hoblitzelle, Dallas, TX 75204, USA.
authors.forename: Erin
authors.identifier: 0000-0002-6986-6190
authors.initials: E
authors.lastname: Hotchkiss
authors.affiliation: GI Cancer Research Laboratory, Baylor University Medical Center, 3500 Gaston Avenue, Suite 250 Hoblitzelle, Dallas, TX 75204, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pérez-Carbonell
authors.affiliation: GI Cancer Research Laboratory, Baylor University Medical Center, 3500 Gaston Avenue, Suite 250 Hoblitzelle, Dallas, TX 75204, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rhees
authors.affiliation: GI Cancer Research Laboratory, Baylor University Medical Center, 3500 Gaston Avenue, Suite 250 Hoblitzelle, Dallas, TX 75204, USA.
authors.forename: Clement Richard
authors.identifier: 0000-0002-8120-5088
authors.initials: CR
authors.lastname: Boland
authors.affiliation: Instituto de Genética Humana, CUCS, Universidad de Guadalajara, Sierra Mojada 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico; Departamento de Clínicas, CUAltos, Universidad de Guadalajara, Carretera a Yahualica Km. 7.5, 47600 Tepatitlán de Morelos, JAL, Mexico.
authors.forename: Melva
authors.initials: M
authors.lastname: Gutiérrez-Angulo