Linked Life Data

14576201

Source:http://linkedlifedata.com/resource/pubmed/id/14576201

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-11-17
pubmed:abstractText
Recent studies have implicated mutations in the ATP-binding cassette transporter A1, ABCA1, as a cause of Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA). We investigated a proband with very low levels of high-density lipoprotein cholesterol (HDL-C, 6 mg/dL) and a history of premature coronary heart disease (CHD). Sequencing of the ABCA1 gene revealed 2 distinct variants. The first mutation was a G5947A substitution (R1851Q). The second mutation was a single-nucleotide deletion of thymidine in a polypyrimidine tract located 33 to 46 bps upstream to the start of exon 47. This mutation does not involve the 3' acceptor splice site and is outside the lariat branchpoint sequence (IVS46: del T -39...-46). Amplification of cDNA obtained in cultured fibroblasts of the proband and affected family member revealed an abnormally spliced cDNA sequence with skipping of exon 47. These variants were not identified in over 400 chromosomes of healthy whites. Compound heterozygotes (n=4) exhibited the lowest HDL-C (11+/-5 mg/dL) and ApoA-I (35+/-15 mg/dL) compared with wild-type (n=25) (HDL-C 51+/-14 mg/dL; ApoA-I 133+/-21 mg/dL) (P<0.0005) or subjects affected with either R1851Q (n=6) (HDL-C 36+/-8; ApoA-I 117+/-19) or IVS46: del T -39...-46 (n=5) (HDL-C 31+9; ApoA-I 115+28 (P<0.01). These data suggest that polypyrimidine tract variation may represent a novel mechanism for altered splicing and exon skipping that is independent of traditional intronic variants as previously identified in acceptor/donor splice regions or the lariat branchpoint domain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1006-12
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14576201-ATP-Binding Cassette Transporters, pubmed-meshheading:14576201-Adult, pubmed-meshheading:14576201-Alternative Splicing, pubmed-meshheading:14576201-Apolipoproteins, pubmed-meshheading:14576201-Cells, Cultured, pubmed-meshheading:14576201-Cholesterol, HDL, pubmed-meshheading:14576201-Coronary Disease, pubmed-meshheading:14576201-DNA Mutational Analysis, pubmed-meshheading:14576201-Exons, pubmed-meshheading:14576201-Fibroblasts, pubmed-meshheading:14576201-Genetic Variation, pubmed-meshheading:14576201-Heterozygote, pubmed-meshheading:14576201-Humans, pubmed-meshheading:14576201-Introns, pubmed-meshheading:14576201-Lipids, pubmed-meshheading:14576201-Lipoproteins, pubmed-meshheading:14576201-Male, pubmed-meshheading:14576201-Mutation, pubmed-meshheading:14576201-Pedigree
pubmed:year
2003
pubmed:articleTitle
Novel polypyrimidine variation (IVS46: del T -39...-46) in ABCA1 causes exon skipping and contributes to HDL cholesterol deficiency in a family with premature coronary disease.
pubmed:affiliation
Department of Medicine, University of Maryland and Veterans Administration Medical Center, Baltimore, Md, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Case Reports, Research Support, Non-U.S. Gov't