dc.contributor.author | Papp, Janos | |
dc.contributor.author | Kovacs, Marietta E | |
dc.contributor.author | Solyom, Szilvia | |
dc.contributor.author | Kasler, Miklos | |
dc.contributor.author | Børresen-Dale, Anne-Lise | |
dc.contributor.author | Olah, Edith | |
dc.date.accessioned | 2015-10-09T02:08:41Z | |
dc.date.available | 2015-10-09T02:08:41Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | BMC Medical Genetics. 2010 Nov 30;11(1):169 | |
dc.identifier.uri | http://hdl.handle.net/10852/46588 | |
dc.description.abstract | Background
Peutz-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.
Methods
Mutation 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.
Results
Thirteen 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.
Conclusions
A 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. | |
dc.language.iso | eng | |
dc.rights | Papp et al. | |
dc.rights | Attribution 2.0 Generic | |
dc.rights.uri | http://creativecommons.org/licenses/by/2.0/ | |
dc.title | High prevalence of germline STK11 mutations in Hungarian Peutz-Jeghers Syndrome patients | |
dc.type | Journal article | |
dc.date.updated | 2015-10-09T02:08:42Z | |
dc.creator.author | Papp, Janos | |
dc.creator.author | Kovacs, Marietta E | |
dc.creator.author | Solyom, Szilvia | |
dc.creator.author | Kasler, Miklos | |
dc.creator.author | Børresen-Dale, Anne-Lise | |
dc.creator.author | Olah, Edith | |
dc.identifier.doi | http://dx.doi.org/10.1186/1471-2350-11-169 | |
dc.identifier.urn | URN:NBN:no-50769 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/46588/1/12881_2010_Article_730.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 169 | |