title: Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families.
abstract: Lynch syndrome (Hereditary nonpolyposis colorectal cancer, HNPCC) is an inherited disease with variable phenotype causing the development of colon cancer and other malignancies. The basis of the disease is believed to be the mismatch repair gene mutations. Genetic screening has been performed among the patients who have undergone surgery for colon cancer at the University of Debrecen, Department of Surgery. Tumor samples of the screened patients were submitted to immunohistochemistry on hMLH1, hMSH2 and hMSH6 genes, microsatellite instability testing, followed by sequencing and multiple ligation dependent probe amplification. Three families were identified with the missense mutation c.143A>C (p.Q48P) of hMLH1 gene. In one of the families a segregation analysis of this particular variant was also accomplished. The segregation analysis revealed a clear correlation between the tumor cases and the occurrence of this mutation. However, none of the analyzed 100 healthy controls demonstrated the same aberration. There is only one published evidence in the literature about the presence of this rare variant in any population. The Gln to Pro switch in the ATPase domain, a conservative region of the hMLH1 gene, creates significant changes in the protein structure. These results indicate that this mutation is the abnormality responsible for the patients' phenotype and it is feasible that this particular aberration occurs more frequently among Hungarian Lynch syndrome patients.
authors.affiliation: Department of Surgery, Medical and Health Science Centre, University of Debrecen, Móricz Zs. Krt. 22, 4032, Debrecen, Hungary. mtanyi@hotmail.com
authors.forename: Miklós
authors.initials: M
authors.lastname: Tanyi
authors.forename: Judit
authors.initials: J
authors.lastname: Olasz
authors.forename: Janos L
authors.initials: JL
authors.lastname: Tanyi
authors.forename: László
authors.initials: L
authors.lastname: Tóth
authors.forename: Péter
authors.initials: P
authors.lastname: Antal-Szalmás
authors.forename: Tamás
authors.initials: T
authors.lastname: Bubán
authors.forename: Csilla
authors.initials: C
authors.lastname: András
authors.forename: Hilda
authors.initials: H
authors.lastname: Urbancsek
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Garami
authors.forename: Orsolya
authors.initials: O
authors.lastname: Csuka
authors.forename: László
authors.initials: L
authors.lastname: Damjanovich
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D005260:Female; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1