Document Detail

A point mutation in ABC1 gene in a patient with severe premature coronary heart disease and mild clinical phenotype of Tangier disease.
MedLine Citation:
PMID:  11257260     Owner:  NLM     Status:  MEDLINE    
The proband is a 50 year-old woman born from a consanguineous marriage. She has been suffering from angina pectoris since the age of 38 and underwent coronary bypass surgery for three-vessel disease at 48. The presence of low plasma levels of total cholesterol and high density lipoprotein (HDL) cholesterol (2.4 and 0.1 mmol/l) and apo AI (<15 mg/dl), associated with corneal lesions and a mild splenomegaly suggested the diagnosis of Tangier disease. However, none of the other features of Tangier disease, including hepatomegaly, anemia and peripheral neuropathy, were present. The analysis of the dinucleotide microsatellites located in chromosome 9q31 region demonstrated that the proband was homozygous for the alleles of D9S53, D9S1784 and D9S1832. The mother and son of the proband, both with low levels of HDL cholesterol, shared one of the proband's haplotypes, whereas neither of these haplotypes was present in the normolipidemic proband's sister. The sequence of ATP-binding cassette transporter 1 (ABC1-1) cDNA obtained by reverse transcription-PCR (RT-PCR) of total RNA isolated from cultured fibroblasts showed that the proband was homozygous for a C>T transition in exon 13, which caused a tryptophane for arginine substitution (R527W). This mutation was confirmed by direct sequencing of exon 13 amplified from genomic DNA. It can be easily screened, as the nucleotide change introduces a restriction site for the enzyme Afl III. R527W substitution occurs in a highly conserved region of the NH2 cytoplasmic domain of ABC1 protein. R527W co-segregates with the low HDL phenotype in the family and was not found in 200 chromosomes from normolipidemic individuals.
S Bertolini; L Pisciotta; M Seri; R Cusano; A Cantafora; L Calabresi; G Franceschini; R Ravazzolo; S Calandra
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Atherosclerosis     Volume:  154     ISSN:  0021-9150     ISO Abbreviation:  Atherosclerosis     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-21     Completed Date:  2001-05-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  599-605     Citation Subset:  IM    
Department of Internal Medicine, University of Genoa, Viale Benedetto XV no. 6, I-16132 Genoa, Italy.
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MeSH Terms
ATP-Binding Cassette Transporters / genetics*
Amino Acid Sequence / genetics
Base Sequence / genetics
Chromosomes, Human, Pair 9 / genetics
Coronary Disease / genetics*,  physiopathology
Genetic Testing
Glycoproteins / genetics*
Middle Aged
Molecular Sequence Data
Mutation / genetics
Point Mutation*
Polymorphism, Genetic
Severity of Illness Index
Tangier Disease / genetics*
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Glycoproteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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