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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1996-9-23
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pubmed:abstractText |
The first step in the splicing of an intron from nuclear precursors of mRNA results in the formation of a lariat structure. A distinct intronic nucleotide sequence, known as the branchpoint region, plays a central role in this process. We here describe a point mutation in such a sequence. Three sisters were shown to suffer from fish-eye disease (FED), a disorder which is caused by mutations in the gene coding for lecithin:cholesterol acyltransferase (LCAT). Sequencing of the LCAT gene of all three probands revealed compound heterozygosity for a missense mutation in exon 4 which is reported to underlie the FED phenotype, and a point mutation located in intron 4 (IVS4:T-22C). By performing in vitro expression of LCAT minigenes and reverse transcriptase PCR on mRNA isolated from leukocytes of the patient, this gene defect was shown to cause a null allele as the result of complete intron retention. In conclusion, we demonstrated that a point mutation in a lariat branchpoint consensus sequence causes a null allele in a patient with FED. In addition, our finding illustrates the importance of this sequence for normal human mRNA processing. Finally, this report provides a widely applicable strategy which ensures fast and effective screening for intronic defects that underlie differential gene expression.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1195397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1303258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1571050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1579465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1681161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1729699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1737840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1861999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-1888769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-2052566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-2174055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-2334724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-2668874,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-2945215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-2977088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-3121980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-3141686,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-3458198,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-3544217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-3649277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-3797244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-4000270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-4337382,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-5100059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-6201719,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-6778896,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-7534458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-7926752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-8240312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-8371071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-8432868,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-8445345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8755645-8675648
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9738
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
358-64
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8755645-Amino Acid Sequence,
pubmed-meshheading:8755645-Base Sequence,
pubmed-meshheading:8755645-Conserved Sequence,
pubmed-meshheading:8755645-Corneal Diseases,
pubmed-meshheading:8755645-DNA Primers,
pubmed-meshheading:8755645-Exons,
pubmed-meshheading:8755645-Female,
pubmed-meshheading:8755645-Heterozygote Detection,
pubmed-meshheading:8755645-Humans,
pubmed-meshheading:8755645-Introns,
pubmed-meshheading:8755645-Male,
pubmed-meshheading:8755645-Middle Aged,
pubmed-meshheading:8755645-Molecular Sequence Data,
pubmed-meshheading:8755645-Pedigree,
pubmed-meshheading:8755645-Phosphatidylcholine-Sterol O-Acyltransferase,
pubmed-meshheading:8755645-Point Mutation,
pubmed-meshheading:8755645-Polymerase Chain Reaction,
pubmed-meshheading:8755645-RNA, Messenger,
pubmed-meshheading:8755645-RNA Precursors
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pubmed:year |
1996
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pubmed:articleTitle |
An intronic mutation in a lariat branchpoint sequence is a direct cause of an inherited human disorder (fish-eye disease).
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pubmed:affiliation |
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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