Genetic and phenotypic characterization of LDL-receptor in patients with a clinical diagnosis of familial hypercholesterolemia: Two novel mutations

2016 ◽  
Vol 252 ◽  
pp. e40
Author(s):  
C. Pavanello ◽  
C. Tarlarini ◽  
S. Penco ◽  
L. Calabresi ◽  
S. Castelnuovo ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Clinical Diagnosis ◽  
Ldl Receptor ◽  
Phenotypic Characterization ◽  
Novel Mutations

scholarly journals Mutation Analysis of the LDL Receptor Gene in Indian Families with Familial Hypercholesterolemia

2011 ◽  
Vol 2 (2) ◽  
pp. 82-86 ◽  
Author(s):  
Suyamindra S Kulkarni ◽  
Suresh Basavraj ◽  
G S Kadakol ◽  
Vandana T ◽  
Amruta Markande ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cholesterol Level ◽  
Mutation Analysis ◽  
Conformational Changes ◽  
Total Cholesterol Level ◽  
Ldl Receptor ◽  
Ldlr Gene ◽  
Novel Mutations ◽  
Study Results ◽  
Myocardial Infraction

Objective: Familial Hypercholesterolemia (FH) is a metabolic disorder inherited as an autosomal dominant trait characterized by an increased plasma low-density lipoprotein (LDL) level. The disease is caused by several different mutations in the LDL receptor (LDLR) gene. Several mutations have been reported in this gene in patients from several ethnic groups. Early identification of individuals carrying the defective gene could be useful in reducing the risk of atherosclerosis and myocardial infraction by the available therapeutic methods. The techniques available for determining the number of the functional LDLR molecules are difficult to carry out and expensive. Our study presents mutation analysis of the LDLR gene in 24 Indian families with FH. Material & Methods: Peripheral blood samples were obtained form individuals after taking informed consent on the condition that each of these individuals had at least one first-degree relative affected with FH. Genomic DNA was isolated, exon-specific intronic primers were designed and used to amplify DNA samples from individuals.PCR products were directly subjected to automated DNA sequencing to detect the mutations. Along with the affected individuals, ten ethnically matched controls were also analyzed to determine the presence of the same mutations. Patients with Nephrotic Syndrome admitted to hospital were excluded from the study. Results: All the 24 patients had total cholesterol level above 300 mg/dl and LDL cholesterol level above 200mg/dl. Sequence analysis of the LDL receptor (LDLR) gene showed 3 novel mutations which have never been reported elsewhere. In exon 10 we reported g.29372_29373insC, which was found in all the 24 patients and was missence mutation coding for C (cysteine) instead of V (valine). Conclusion: Our study reported 3 novel mutations in 24 Indian families. These novel mutations are predicted to produce change in the amino acid and thus leading to the conformational changes in the structure of LDLR protein. Change in the LDLR protein makes the LDL receptor unable to transport the cholesterol in to the cell and hence cholesterol starts accumulating in the blood stream and leads to FH. Key Words: Familial Hypercholesterolemia; Mutation analysis; LDL Receptor geneDOI: http://dx.doi.org/10.3126/ajms.v2i2.4573Asian Journal of Medical Sciences 2 (2011) 82-86

Identification of two novel mutations of the LDL receptor gene in two Italian families with familial hypercholesterolemia

2015 ◽  
Vol 241 (1) ◽  
pp. e114
Author(s):  
K. Garlaschelli ◽  
F. Pellegatta ◽  
A. Baragetti ◽  
L. Grigore ◽  
A. Pirillo ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Receptor Gene ◽  
Ldl Receptor ◽  
Novel Mutations

scholarly journals Characterization of Atherosclerosis Formation in a Murine Model of Type IIa Human Familial Hypercholesterolemia

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Chiharu Miyajima ◽  
Takayuki Iwaki ◽  
Kazuo Umemura ◽  
Victoria A. Ploplis ◽  
Francis J. Castellino
Keyword(s):  
Familial Hypercholesterolemia ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Genetic Model ◽  
Ldl Receptor ◽  
Normal Diet ◽  
Atherosclerotic Plaques ◽  
Key Features ◽  
Very High

A murine genetic model of LDL-cholesterol- (LDL-C-) driven atherosclerosis, based on complete deficiencies of both the LDL-receptor (Ldlr-/-) and key catalytic component of an apolipoprotein B-edisome complex (Apobec1-/-), which converts apoB-100 to apoB-48, has been extensively characterized. These gene deficiencies allow high levels of apoB-100 to be present and inefficiently cleared, thus leading to very high levels of LDL-C in mice on a normal diet. Many key features of atherosclerotic plaques observed in human familial hypercholesterolemia are found in these mice as they are allowed to age through 72 weeks. The general characteristics include the presence of high levels of LDL-C in plasma and macrophage-related fatty streak formation in the aortic tree, which progressively worsens with age. More specifically, plaque found in the aortic sinuses contains a lipid core with relatively high numbers of macrophages and a smooth muscle cell α-actin- and collagen-containing cap, which thins with age. These critical features of plaque progression suggest that the Ldlr-/-/Apobec1-/- mouse line presents a superior model of LDL-C-driven atherosclerosis.

Phenotypic characterization of a patient homozygous for the D558N LDL receptor gene mutation

2008 ◽  
Vol 50 (5) ◽  
pp. 388-392 ◽  
Author(s):  
H. K. Jensen ◽  
L. G. Jensen ◽  
F. Heath ◽  
F. Melsen ◽  
P. S. Hansen ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Receptor Gene ◽  
Ldl Receptor ◽  
Phenotypic Characterization

C11 Two novel mutations in exon 4 of LDL-receptor gene causing familial hypercholesterolemia (FH) in northern Italy

1999 ◽  
Vol 145 ◽  
pp. S3
Author(s):  
S Bertolini ◽  
M Rolleri ◽  
G Trovatello ◽  
Masturzo ◽  
N Elicio ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Receptor Gene ◽  
Ldl Receptor ◽  
Northern Italy ◽  
Novel Mutations ◽  
Exon 4
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