High prevalence of germline STK11mutations in Hungarian Peutz-Jeghers Syndrome patients

BMC Medical Genetics

Research Article

Anne-Lise Børresen-Dale¹  Miklos Kasler²  Marietta Eva Kovacs³  Edith Olah³  Janos Papp³  Szilvia Solyom⁴ 

[1] Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway;Institute for Clinical Medicine, Faculty of Medicine, Univeristy of Oslo, Norway;Department of Head and Neck Surgery, National Institute of Oncology, Budapest, Hungary;Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary;Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary;Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, Oulu, Finland;

关键词: Genomic Deletion;    Hamartomatous Polyp;    STK11 Gene;    Large Genomic Deletion;    Mucocutaneous Pigmentation;   

DOI  :  10.1186/1471-2350-11-169

 received in 2010-07-13, accepted in 2010-11-30,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPeutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disease characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. The genetic predisposition for PJS has been shown to be associated with germline mutations in the STK11/LKB1 tumor suppressor gene. The aim of the present study was to characterize Hungarian PJS patients with respect to germline mutation in STK11/LKB1 and their association to disease phenotype.MethodsMutation screening of 21 patients from 13 PJS families were performed using direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Comparative semi-quantitative sequencing was applied to investigate the mRNA-level effects of nonsense and splice-affecting mutations.ResultsThirteen different pathogenic mutations in STK11, including a high frequency of large genomic deletions (38%, 5/13), were identified in the 13 unrelated families studied. One of these deletions also affects two neighboring genes (SBNO2 and GPX4), located upstream of STK11, with a possible modifier effect. The majority of the point mutations (88%, 7/8) can be considered novel. Quantification of the STK11 transcript at the mRNA-level revealed that the expression of alleles carrying a nonsense or frameshift mutation was reduced to 30-70% of that of the wild type allele. Mutations affecting splice-sites around exon 2 displayed an mRNA processing pattern indicative of co-regulated splicing of exons 2 and 3.ConclusionsA combination of sensitive techniques may assure a high (100%) STK11 mutation detection frequency in PJS families. Characterization of mutations at mRNA level may give a deeper insight into the molecular consequences of the pathogenic mutations than predictions made solely at the genomic level.

【 授权许可】

Unknown   
© Papp et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.