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Titolo:
Mutation screening at the RNA level of the STK11/LKB-1 gene in Peutz-Jeghers syndrome reveals complex splicing abnormalities and a novel mRNA isoform(STK11 c.597 (boolean AND) 598insIVS4)
Autore:
Abed, AA; Gunther, K; Kraus, C; Hohenberger, W; Ballhausen, WG;
Indirizzi:
Univ Halle Wittenberg, Bioctr, MGO, Dept Internal Med, D-06120 Halle Saale, Germany Univ Halle Wittenberg Halle Saale Germany D-06120 0 Halle Saale, Germany Univ Erlangen Nurnberg, Dept Surg, Erlangen, Germany Univ Erlangen Nurnberg Erlangen Germany g, Dept Surg, Erlangen, Germany Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany Univ Erlangen Nurnberg Erlangen Germany D-8520 D-8520 Erlangen, Germany
Titolo Testata:
HUMAN MUTATION
fascicolo: 5, volume: 18, anno: 2001,
pagine: 397 - 410
SICI:
1059-7794(2001)18:5<397:MSATRL>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSLATIONAL TERMINATION EFFICIENCY; SERINE/THREONINE PROTEIN-KINASE; POLYPOSIS-COLI GENE; MESSENGER-RNA; GERMLINE MUTATIONS; ADENOMATOUS POLYPOSIS; TUMOR-SUPPRESSOR; IN-VIVO; LKB1; EXPRESSION;
Keywords:
methylation; Peutz-Jeghers syndrome (PJS); protein truncation test; RNA screening; serine/threonine protein kinase 11; serine-threonine protein kinase 11 (STK11); LKB1; mutation screening;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Ballhausen, WG Univ Halle Wittenberg, Bioctr, MGO, Dept Internal Med, Weinbergweg 22, D-06120 Halle Saale, Germany Univ Halle Wittenberg Weinbergweg 22 Halle Saale Germany D-06120
Citazione:
A.A. Abed et al., "Mutation screening at the RNA level of the STK11/LKB-1 gene in Peutz-Jeghers syndrome reveals complex splicing abnormalities and a novel mRNA isoform(STK11 c.597 (boolean AND) 598insIVS4)", HUM MUTAT, 18(5), 2001, pp. 397-410

Abstract

This study was intended to evaluate a diagnostic reverse transcriptase polymerase chain reaction based protein-truncation test for the identificationof germline mutations in the serine/threonine protein kinase 11 (STK11, also designated LKB1) gene in Peutz-Jeghers syndrome (PJS). Our data exemplify that the inactivation of STK11 can be due to unusual disturbances in splicing regulation which result in truncations of the protein. However, nonsense mediated mRNA decay must be blocked with puromycin to detect shortened STK11 gene products contained in the leucocytic mRNA pool of PJS patients. Interestingly, two mutations escaped from detection by exon sequencing techniques with usual flanking PCR primers, since alterations were located rightin the middle of intronic sequences. We describe a compound heterozygous PJS patient who carried two different mutations in intron 1 on separate alleles. Each of the two mutations was transmitted individually to one of his two children. In the course of our RNA based analyses we detected high levelexpression of a novel STK11/LKB1 mRNA variant retaining intron 4 (STK11 c.597(boolean AND)598insIVS4) in various tissues. This mRNA isoform was initiated from an alternative transcription regulatory region as revealed by primer extension analyses even in cell lines with complete methylation of the normal promoter. As a consequence of novel mutational mechanisms identifiedwe discuss the impact of RNA based strategies for the detection of germinal STK11 mutations in PJS. Hum Mutat 18:397-410, 2001. (C) 2001 Wiley-Liss, Inc.

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Documento generato il 10/04/20 alle ore 02:12:24