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Disruption of an exon splicing enhancer in exon 3 of MLH1 is the cause of HNPCC in a Quebec family.

https://arctichealth.org/en/permalink/ahliterature174535
Source
J Med Genet. 2006 Feb;43(2):153-6
Publication Type
Article
Date
Feb-2006
Author
S. McVety
L. Li
P H Gordon
G. Chong
W D Foulkes
Source
J Med Genet. 2006 Feb;43(2):153-6
Date
Feb-2006
Language
English
Publication Type
Article
Keywords
Adaptor Proteins, Signal Transducing
Animals
COS Cells
Carrier Proteins - genetics
Cercopithecus aethiops
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
Exons - genetics
Humans
Nuclear Proteins - genetics
Point Mutation - genetics
Quebec
RNA Splice Sites - genetics
RNA Splicing - genetics
Regulatory Sequences, Ribonucleic Acid - genetics
Abstract
A 3 bp deletion located at the 5' end of exon 3 of MLH1, resulting in deletion of exon 3 from RNA, was recently identified.
That this mutation disrupts an exon splicing enhancer (ESE) because it occurs in a purine-rich sequence previously identified as an ESE in other genes, and ESEs are often found in exons with splice signals that deviate from the consensus signals, as does the 3' splice signal in exon 3 of MLH1.
The 3 bp deletion and several other mutations were created by polymerase chain reaction mutagenesis and tested using an in vitro splicing assay. Both mutant and wild type exon 3 sequences were cloned into an exon trapping vector and transiently expressed in Cos-1 cells.
Analysis of the RNA indicates that the 3 bp deletion c.213_215delAGA (gi:28559089, NM_000249.2), a silent mutation c.216T-->C, a missense mutation c.214G-->C, and a nonsense mutation c.214G-->T all cause varying degrees of exon skipping, suggesting the presence of an ESE at the 5' end of exon 3. These mutations are situated in a GAAGAT sequence 3 bp downstream from the start of exon 3.
The results of the splicing assay suggest that inclusion of exon 3 in the mRNA is ESE dependent. The exon 3 ESE is not recognised by all available motif scoring matrices, highlighting the importance of RNA analysis in the detection of ESE disrupting mutations.
Notes
Cites: Genes Chromosomes Cancer. 1999 Dec;26(4):372-510534773
Cites: Mol Cell Biol. 1999 Jan;19(1):261-739858550
Cites: Mol Cell Biol. 2000 Nov;20(22):8303-1811046128
Cites: Cancer Res. 2001 Oct 1;61(19):7020-411585727
Cites: Hum Mutat. 2002 Feb;19(2):108-1311793469
Cites: Nat Rev Genet. 2002 Apr;3(4):285-9811967553
Cites: Science. 2002 Jul 5;297(5578):108-1012098701
Cites: Genes Dev. 2002 Jul 15;16(14):1743-5312130534
Cites: Genes Dev. 2002 Jul 15;16(14):1754-912130535
Cites: Science. 2002 Aug 9;297(5583):1007-1312114529
Cites: J Med Genet. 2002 Oct;39(10):747-5012362032
Cites: Biochem J. 2003 Apr 1;371(Pt 1):183-912513688
Cites: Am J Hum Genet. 2003 May;72(5):1088-10012658575
Cites: Hum Mol Genet. 2003 May 15;12(10):1111-2012719375
Cites: Nucleic Acids Res. 2003 Jul 1;31(13):3568-7112824367
Cites: J Biol Chem. 2003 Jul 18;278(29):26580-812732620
Cites: Am J Hum Genet. 2003 Nov;73(5):1157-6114526391
Cites: J Med Genet. 2004 Jun;41(6):e7215173238
Cites: J Med Genet. 2004 Jul;41(7):e9515235038
Cites: Hum Mutat. 2004 Sep;24(3):27215300854
Cites: Nat Rev Cancer. 2004 Oct;4(10):769-8015510158
Cites: J Biol Chem. 1993 Apr 15;268(11):8366-758463344
Cites: Science. 1993 Apr 9;260(5105):219-228385799
Cites: Genes Dev. 1993 Dec;7(12A):2405-178253386
Cites: Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2642-67708698
Cites: Genes Dev. 1996 Jul 1;10(13):1569-798682289
Cites: J Clin Invest. 1997 Nov 1;100(9):2204-109410897
Cites: Trends Biochem Sci. 2000 Mar;25(3):106-1010694877
PubMed ID
15923275 View in PubMed
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