The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Asier Benito-VicenteMafalda Bourbon

Abstract

Familial hypercholesterolemia (FH) is one of the most common monogenic disorders, and the high concentrations of low-density lipoprotein (LDL) cholesterol presented since birth confers on these patients an increased cardiovascular risk. More than 1,600 alterations have been described in the LDL receptor gene (LDLR), but a large number need to be validated as mutations causing disease to establish a diagnosis of FH. This study aims to characterize, both at the phenotypic and genotypic levels, families with a clinical diagnosis of FH and present evidence for the importance of the integration of clinical, molecular, and functional data for the correct diagnosis of patients with FH. A detailed analysis of the phenotype and genotype presented by 55 families with 13 different alterations in the LDLR was conducted. For eight of these, an extensive functional characterization was performed by flow cytometry, confocal microscopy, and reverse transcriptase polymerase chain reaction. Carriers of neutral alterations presented a significantly lower incidence of premature cardiovascular disease, lower levels of atherogenic lipoproteins and a large number of these individuals had LDL-cholesterol values below the 75(th) percentile. presented a...Continue Reading

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Citations

Jul 22, 2015·Journal of Atherosclerosis and Thrombosis·Raul D SantosAna P M Chacra
Apr 26, 2011·Nutrition & Metabolism·Akl C Fahed, Georges M Nemer
Feb 9, 2017·Current Opinion in Lipidology·Mafalda BourbonEric J Sijbrands
Nov 9, 2016·Journal of Medical Genetics·Sarah LeighSteve E Humphries
Jun 7, 2019·Molecular Diagnosis & Therapy·Ye-Xuan CaoJian-Jun Li
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Nov 7, 2019·Atherosclerosis·Andrea GomezLuis Cuniberti
Jun 25, 2021·Atherosclerosis·Ana Catarina AlvesMafalda Bourbon

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