Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families

Miklós Tanyi, Judit Olasz, Janos L. Tanyi, L. Tóth, P. Antal-Szalmás, Tamás Bubán, C. András, Hilda Urbancsek, Zoltán Garami, O. Csuka, László Damjanovich

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)519-524
Number of pages6
JournalFamilial Cancer
Volume11
Issue number3
DOIs
Publication statusPublished - Sep 2012

Fingerprint

Hereditary Nonpolyposis Colorectal Neoplasms
Mutation
Colonic Neoplasms
Genes
Phenotype
Neoplasms
Microsatellite Instability
DNA Mismatch Repair
Genetic Testing
Missense Mutation
Ligation
Adenosine Triphosphatases
Immunohistochemistry
Population
Proteins

Keywords

  • HMLH1
  • Hungarian
  • Lynch syndrome
  • MMR
  • MSI

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Oncology
  • Genetics(clinical)

Cite this

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families. / Tanyi, Miklós; Olasz, Judit; Tanyi, Janos L.; Tóth, L.; Antal-Szalmás, P.; Bubán, Tamás; András, C.; Urbancsek, Hilda; Garami, Zoltán; Csuka, O.; Damjanovich, László.

In: Familial Cancer, Vol. 11, No. 3, 09.2012, p. 519-524.

Research output: Contribution to journalArticle

Tanyi, Miklós ; Olasz, Judit ; Tanyi, Janos L. ; Tóth, L. ; Antal-Szalmás, P. ; Bubán, Tamás ; András, C. ; Urbancsek, Hilda ; Garami, Zoltán ; Csuka, O. ; Damjanovich, László. / Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families. In: Familial Cancer. 2012 ; Vol. 11, No. 3. pp. 519-524.
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