1/14. Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene.We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L. kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous for a T-deletion in exon 26, which converts tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an apoB-75.7 carrier, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.- - - - - - - - - - ranking = 1keywords = atherosclerosis (Clic here for more details about this article) |
2/14. Clinical variant of tangier disease in japan: mutation of the ABCA1 gene in hypoalphalipoproteinemia with corneal lipidosis.Despite progress in molecular characterization, specific diagnoses of disorders belonging to a group of inherited hypoalphalipoproteinemias, i.e., apolipoprotein AI deficiency, lecithin-cholesterol acyltransferase deficiency, tangier disease (TD), and familial high-density lipoprotein (HDL) deficiency, remain difficult on a purely clinical basis. Several TD patients were recently found to be homozygous for mutations in the ABCA1 gene. We have documented here a clinical variant of TD in a Japanese patient who manifested corneal lipidosis and premature coronary artery disease as well as an almost complete absence of HDL-cholesterol, by identifying a novel homozygous ABCA1 mutation (R1680W). We propose that patients with apparently isolated HDL deficiency who are found to carry ABCA1 mutations may in fact belong to a category of TD patients whose phenotypic features are only partially expressed, and that a number of hidden clinical variants of TD might exist among other HDL deficiency patients who have escaped correct clinical diagnosis.- - - - - - - - - - ranking = 0.47096118362771keywords = artery disease, artery (Clic here for more details about this article) |
3/14. ABCA1(alabama): a novel variant associated with HDL deficiency and premature coronary artery disease.The ATP-binding cassette transporter, ABCA1, is a member of the ABC superfamily of proteins involved in the active transport of substrates across cellular membranes. Recent studies have implicated mutations in ABCA1 as the cause of tangier disease (TD) and familial hypoalphalipoproteinemia (FHA). To evaluate the molecular basis of low high density lipoprotein (HDL) in a family with premature coronary artery disease, single strand conformational polymorphism analysis was performed for all coding regions and splice site junctions of ABCA1 with the genomic dna of the proband. The proband and affected individuals were heterozygotes for C254T with proline converted to leucine (P85L). This mutation was not identified in over 400 chromosomes of healthy subjects. In the FHA kindred, family members heterozygous for the ABCA1 variant also exhibited corresponding low levels of HDL cholesterol. These data confirm recent data that a single defective allele in ABCA1 may be associated with reduced HDL cholesterol and FHA.- - - - - - - - - - ranking = 2.3548059181385keywords = artery disease, artery (Clic here for more details about this article) |
4/14. coronary artery bypass grafting for a patient with tangier disease.A 56-year-old man with tangier disease suffering from angina pectoris due to triple-vessel coronary artery disease evidenced extremely low blood high-density lipoprotein of 1 mg/dl, a specific laboratory indicator of this rare genetic disorder of lipid metabolism, considered to accompany juvenile arteriosclerosis. Because of the calcified ascending aorta, we conducted combined minimally invasive coronary artery bypass (CAB) for the left anterior descending coronary artery and percutaneous transluminal coronary angioplasty for other coronary artery lesions initially instead of conventional coronary artery bypass grafting. Angina recurred, however, due to refractory restenosis of the left circumflex coronary artery lesion. Two years later, we redid the CAB, grafting the free right internal thoracic artery from the functional left internal thoracic artery sequentially onto obtuse marginal and posterolateral coronary arteries. The patient returned to work angina-free.- - - - - - - - - - ranking = 0.49275757163436keywords = artery disease, artery (Clic here for more details about this article) |
5/14. The heart in tangier disease. Severe coronary atherosclerosis with near absence of high-density lipoprotein cholesterol.Cardiac necropsy findings are described in a 72-year-old man with tangier disease whose plasma total cholesterol levels averaged 70 mg/dL, low-density lipoprotein cholesterol level was 45 mg/dL, and high-density lipoprotein cholesterol level was 1.4 mg/dL, and who had coronary artery bypass grafting for severe atherosclerotic coronary artery disease. At necropsy, 24 of the 72 (33%) 5-mm segments of the 4 major (right, left main, left anterior descending, and left circumflex) native coronary arteries and 4 of the 27 (15%) 5-mm segments of the saphenous vein aortocoronary bypass conduits were narrowed by more than 75% in cross-sectional area by atherosclerotic plaques. The plaques were composed primarily (91% to 97%) of fibrous tissue. Oil red O staining, polarized light microscopy, and electron microscopy revealed cholesterol deposits in the plaques and in the walls of coronary arteries, saphenous vein grafts, and aorta. Such deposits also were found in foam cells of histiocytic origin, fibroblasts in all four cardiac valves, and in schwann cells of cardiac nerves.- - - - - - - - - - ranking = 4.4729426734465keywords = atherosclerosis, artery disease, artery (Clic here for more details about this article) |
6/14. Combined monogenic hypercholesterolemia and hypoalphalipoproteinemia caused by mutations in LDL-R and LCAT genes.We studied a three generation family with co-dominant monogenic hypercholesterolemia and hypoalphalipoproteinemia. The proband, a 48 year-old male, was found to be heterozygous for a previously reported mutation in LDL receptor (LDL-R) gene (IVS15-3 c>a) and a novel mutation in exon 6 of lecithin cholesterol acyltransferase (LCAT) gene (c.803 G>A) causing a non-synonymous amino acid substitution (p.R244H). These mutations segregated independently in the family. The LDL-R mutation was associated with high levels of LDL-C (6.20-9.85 mmol/L) and apo B (170-255 mg/dL), comparable to those previously reported in carriers of the same mutation. The LCAT mutation was associated with low levels of HDL-C (0.67-0.80 mmol/L) and apo A-I (96-110 mg/dL). The proband had reduced LCAT function, as measured by cholesterol esterification rate (29 nmol/(mL/h) versus 30-60 nmol/(mL/h)), LCAT activity (10 nmol/(mL/h) versus 20-55 nmol/(mL/h)) and LCAT mass (2.87 microg/mL versus 3.1-6.7 microg/mL). Carriers of LCAT mutation had lower LCAT activity and a tendency to reduced cholesterol esterification rate (CER) and LCAT mass as compared to non-carrier family members. The LCAT mutation was not found in 80 control subjects and 60 patients with primary hypoalphalipoproteinemia. Despite the unfavourable lipoprotein profile, the proband had only mild clinical signs of atherosclerosis. This unexpected finding is probably due to the intensive lipid lowering treatment the patient has been on over the last decade.- - - - - - - - - - ranking = 1keywords = atherosclerosis (Clic here for more details about this article) |
7/14. A 'Fish-eye disease' familial condition with massive corneal opacities and hypoalphalipoproteinaemia: clinical, biochemical and genetic features.A Caucasian family of mediterranean origin comprising a patient whose parents were first cousins, his wife and their three children, and his two sisters have been studied. The patient and his two daughters were afflicted with the same corneal opacities and hypoalphalipoproteinaemia. The disease was shown to be transmitted as a non-sex-linked recessive trait. The corneal opacities develop at the end of the second decade of life and consist of numerous minute greyish dots in the entire corneal stroma that give the cornea a misty appearance. Vision slowly deteriorated from 40 years of age. At about 50 years of age, except in one of the two daughters who showed Marfanoid syndrome, the three patients had good general health and no symptoms of atherosclerosis. Biochemical investigations showed hypoalphalipoproteinaemia (with a faint fast-moving HDL band on polyacrylamide gel gradient electrophoresis and small arcs of HDL2 and HDL3 of low mobility determined by agarose gel immunoelectrophoresis), low total cholesterol (3.5-4.9 mmol l-1), slightly decreased cholesteryl ester/total cholesterol ratio (0.52-0.63), extremely low HDL cholesterol (0.20-0.21 mmol l-1), mild hypertriglyceridaemia (1.94-3.80 mmol l-1), and striking deficiency in apo A-I and apo A-II (0.45-0.72, 0.08-0.16 g l-1, respectively). The esterification of HDL cholesterol was low while that of LDL and VLDL was nearly normal. Other laboratory values were normal. The HDL subspecies and major apolipoprotein isoforms have been studied to differentiate FED from tangier disease, LCAT deficiency, as Apo A-I, A-II, C-II, C-III deficiencies and variants.(ABSTRACT TRUNCATED AT 250 WORDS)- - - - - - - - - - ranking = 1keywords = atherosclerosis (Clic here for more details about this article) |
8/14. bile lipid composition and haemostatic variables in a case of high density lipoprotein deficiency (tangier disease).A 62-year-old man with clinical and biochemical findings consistent with homozygous tangier disease is presented. Widespread atherosclerosis was present. bile lipid analysis showed a low molar percentage of cholesterol with a low saturation index. The data suggest that high density lipoprotein cholesterol may act as a preferential precursor of biliary cholesterol. Coagulation and platelet studies indicated that the patient's platelets were hyper-responsive to aggregating agents and produced an increased amount of thromboxane b2. A platelet storage pool deficiency was also found.- - - - - - - - - - ranking = 1keywords = atherosclerosis (Clic here for more details about this article) |
9/14. Hypoalpha-hyperbeta-lipoproteinemia in a patient with coronary artery disease and occlusive peripheral arterial disease.This study describes a variant of hypo-alpha-lipoproteinemia in a 57-year-old male patient. The total plasma cholesterol level was 258 mg/dl with 64% in esterified form. The concentration of triglycerides was 205 mg/dl. The lipoprotein electrophoretic pattern revealed the absence of alpha-lipoproteins, whereas the other lipoproteins showed an intermediate electrophoretic mobility. The concentration of HDL cholesterol (heparin: MgCl2 precipitation) was extremely low (3 mg/dl). The activity of lecithin; cholesterol acyltransferase (LCAT) and the postheparinlipolytic activity were within the normal range. Determination of apolipoproteins revealed a marked deficiency of both apoprotein A-I (17 mg/dl) and apolipoprotein a-ii (11 mg/dl). The concentration of apolipoprotein-B was elevated (186 mg/dl). Unlike the clinical manifestations of tangier disease, our patient did not show skin lesion, abnormal tonsils, hepatosplenomegaly, peripheral neurologic abnormalities or corneal deposits. Also in contrast to tangier disease our patient had coronary artery disease with myocardial infarction accompanied with severe occlusive peripheral arterial disease.- - - - - - - - - - ranking = 2.3548059181385keywords = artery disease, artery (Clic here for more details about this article) |
10/14. Characterization of atherosclerosis in a patient with familial high-density lipoprotein deficiency.We describe the cardiovascular state of a 60-year-old homozygous patient with familial HDL deficiency (tangier disease). The patient was examined by coronary angiography and intravascular ultrasound because of chest pain at rest and on exertion. We found a normal left ventricular function, moderately diffuse coronary sclerosis without stenosis and no critical stenosis of peripheral arteries. Intravascular ultrasound revealed the three layer appearance of arterial intima, media and adventitia with normal thickness. No calcified plaques or intimal hyperplasia could be detected apart from a single, discrete atherosclerotic lesion in one iliac artery segment. Concentric non-occlusive atherosclerotic lesions which are readily detectable with intravascular ultrasound were not found. The lack of severe atherosclerosis was remarkable insofar as massive foam cell formation and the virtually complete absence of circulating HDL is characteristic of tangier disease and has been previously demonstrated in this patient. Our findings suggest that HDL deficiency and foam cell formation in tangier disease are not necessarily associated with accelerated development of atherosclerosis.- - - - - - - - - - ranking = 6.0019814898188keywords = atherosclerosis, artery (Clic here for more details about this article) |
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