Partial duplication of the EGF precursor homology domain of the LDL-receptor protein causing familial hypercholesterolemia (FH-Salerno).

A new technique has been developed to identify low-density-lipoprotein (LDL) receptors on nitrocellulose membranes, after transfer from SDS/polyacrylamide gels, by ligand blotting with biotin-modified LDL. Modification with biotin hydrazide of periodate-oxidized lipoprotein sugar residues does not affect the ability of the lipoprotein to bind to the LDL receptor. Bound lipoprotein is detected with high sensitivity by a streptavidin-biotin-peroxidase complex, and thus this method eliminates the need for specific antibodies directed against the ligand. The density of the bands obtained is proportional to the amount of pure LDL receptor protein applied to the SDS/polyacrylamide gel, so that it is possible to quantify LDL receptor protein in cell extracts. Biotin can be attached to other lipoproteins, for example very-low-density lipoproteins with beta-mobility, and thus the method will be useful in the identification and isolation of other lipoprotein receptors.

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A combined LDL receptor/LDL receptor adaptor protein 1 mutation as the cause for severe familial hypercholesterolemia

Gene ◽

10.1016/j.gene.2013.03.034 ◽

2013 ◽

Vol 521 (1) ◽

pp. 200-203 ◽

Cited By ~ 14

Author(s):

Muhidien Soufi ◽

Stephan Rust ◽

Michael Walter ◽

Juergen R. Schaefer

Keyword(s):

Familial Hypercholesterolemia ◽

Ldl Receptor ◽

Adaptor Protein

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Long-Distance PCR-based Screening for Large Rearrangements of the LDL Receptor Gene in Korean Patients with Familial Hypercholesterolemia

Clinical Chemistry ◽

10.1093/clinchem/45.9.1424 ◽

1999 ◽

Vol 45 (9) ◽

pp. 1424-1430 ◽

Cited By ~ 17

Author(s):

Sung Han Kim ◽

Ji Hyun Bae ◽

Jae Jin Chae ◽

Un Kyung Kim ◽

Seong-Joon Choe ◽

...

Keyword(s):

Sequence Analysis ◽

Familial Hypercholesterolemia ◽

Receptor Gene ◽

Blot Hybridization ◽

Screening Method ◽

Ldl Receptor ◽

Southern Blot Hybridization ◽

Long Distance ◽

Large Rearrangements ◽

Long Distance Pcr

Abstract Background: The LDL receptor is a cell-surface protein that regulates plasma cholesterol by specific uptake of LDL particles from the blood circulation. Familial hypercholesterolemia (FH) results from defective catabolism of LDL, which is caused by mutations in the LDL-receptor gene. Methods: For the rapid and reliable detection of large rearrangements in the LDL-receptor gene, we established a screening method based on long-distance PCR as an alternative to Southern-blot hybridization. Using long-distance PCR, 45 unrelated Korean subjects heterozygous for FH were screened to assess the frequency and nature of major structural rearrangements in the LDL-receptor gene. Results: Two different deletion mutations, FH6 (same type as FH3 and FH311) and FH 32, were detected in four families by long-distance PCR. Detailed restriction mapping and sequence analysis showed that FH6 was a 5.71-kb deletion extending from intron 8 to intron 12 and that FH32 was a 2-kb deletion extending from intron 6 to intron 7. Sequence analysis for the breakpoints of all deletions detected in Korean FH patients showed that only the left arms of the Alu repetitive sequences were involved in the deletion event. Conclusions: The screening method based on long-distance PCR provides a powerful strategy for the detection of large rearrangements in the LDL-receptor gene and is a rapid and reliable screening alternative to Southern-blot hybridization.

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5938Efficacy of evinacumab in homozygous familial hypercholesterolemia patients with null or non-null LDL-receptor mutations and on various background therapies

European Heart Journal ◽

10.1093/eurheartj/ehx493.5938 ◽

2017 ◽

Vol 38 (suppl_1) ◽

Author(s):

G.K. Hovingh ◽

D.A. Gipe ◽

Z. Ahmad ◽

M. Cuchel ◽

P. Shah ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Ldl Receptor ◽

Homozygous Familial Hypercholesterolemia

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Familial Hypercholesterolemia: Three “under” (Understood, Underdiagnosed, and Undertreated) Disease

Cardiovascular Risk Factors in Pathology ◽

10.5772/intechopen.93042 ◽

2021 ◽

Author(s):

Vladimir O. Konstantinov

Keyword(s):

Familial Hypercholesterolemia ◽

Time Course ◽

Ldl Cholesterol ◽

Genetic Disorders ◽

Receptor Gene ◽

Ldl Receptor ◽

Hdl Cholesterol ◽

Blood Cholesterol ◽

Healthy Population ◽

Loss Of Function

Familial hypercholesterolemia (FH) is one of the most prevalent genetic disorders leading to premature atherosclerosis and coronary heart disease. The main cause of FH is a mutation in the LDL-receptor gene that leads to loss of function of these receptors causing high levels of blood cholesterol. The diagnosis of FH is not very easy. Wide screenings are needed to reveal high levels of LDL cholesterol among “healthy” population. If the patient has MI or stroke at an early age, high levels of LDL cholesterol, and tendon xanthomas, the diagnosis of FH becomes much more clear. Genetic testing is a gold standard in the diagnosis of FH. There are several factors, influencing the time course of FH. Smoking males with low levels of HDL cholesterol have an extremely higher risk of death than nonsmoking females with high HDL cholesterol. Management of FH includes low cholesterol diet, statin and ezetimibe treatment, PCSK inhibitors, and LDL aphaeresis. Early and effective treatment influences much the prognosis in FH patients.

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