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Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is one of the most common autosomal, dominantly inherited diseases affecting cholesterol metabolism, which, in the absence of treatment, leads to the development of cardiovascular complications. The disease is still underdiagnosed, even though an early diagnosis wo...

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Autores principales: Madar, László, Juhász, Lilla, Szűcs, Zsuzsanna, Kerkovits, Lóránt, Harangi, Mariann, Balogh, István
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775528/
https://www.ncbi.nlm.nih.gov/pubmed/35052492
http://dx.doi.org/10.3390/genes13010153
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author Madar, László
Juhász, Lilla
Szűcs, Zsuzsanna
Kerkovits, Lóránt
Harangi, Mariann
Balogh, István
author_facet Madar, László
Juhász, Lilla
Szűcs, Zsuzsanna
Kerkovits, Lóránt
Harangi, Mariann
Balogh, István
author_sort Madar, László
collection PubMed
description Familial hypercholesterolemia (FH) is one of the most common autosomal, dominantly inherited diseases affecting cholesterol metabolism, which, in the absence of treatment, leads to the development of cardiovascular complications. The disease is still underdiagnosed, even though an early diagnosis would be of great importance for the patient to receive proper treatment and to prevent further complications. No studies are available describing the genetic background of Hungarian FH patients. In this work, we present the clinical and molecular data of 44 unrelated individuals with suspected FH. Sequencing of five FH-causing genes (LDLR, APOB, PCSK9, LDLRAP1 and STAP1) has been performed by next-generation sequencing (NGS). In cases where a copy number variation (CNV) has been detected by NGS, confirmation by multiplex ligation-dependent probe amplification (MLPA) has also been performed. We identified 47 causal or potentially causal (including variants of uncertain significance) LDLR and APOB variants in 44 index patients. The most common variant in the APOB gene was the c.10580G>A p.(Arg3527Gln) missense alteration, this being in accordance with literature data. Several missense variants in the LDLR gene were detected in more than one index patient. LDLR variants in the Hungarian population largely overlap with variants detected in neighboring countries.
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spelling pubmed-87755282022-01-21 Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia Madar, László Juhász, Lilla Szűcs, Zsuzsanna Kerkovits, Lóránt Harangi, Mariann Balogh, István Genes (Basel) Article Familial hypercholesterolemia (FH) is one of the most common autosomal, dominantly inherited diseases affecting cholesterol metabolism, which, in the absence of treatment, leads to the development of cardiovascular complications. The disease is still underdiagnosed, even though an early diagnosis would be of great importance for the patient to receive proper treatment and to prevent further complications. No studies are available describing the genetic background of Hungarian FH patients. In this work, we present the clinical and molecular data of 44 unrelated individuals with suspected FH. Sequencing of five FH-causing genes (LDLR, APOB, PCSK9, LDLRAP1 and STAP1) has been performed by next-generation sequencing (NGS). In cases where a copy number variation (CNV) has been detected by NGS, confirmation by multiplex ligation-dependent probe amplification (MLPA) has also been performed. We identified 47 causal or potentially causal (including variants of uncertain significance) LDLR and APOB variants in 44 index patients. The most common variant in the APOB gene was the c.10580G>A p.(Arg3527Gln) missense alteration, this being in accordance with literature data. Several missense variants in the LDLR gene were detected in more than one index patient. LDLR variants in the Hungarian population largely overlap with variants detected in neighboring countries. MDPI 2022-01-15 /pmc/articles/PMC8775528/ /pubmed/35052492 http://dx.doi.org/10.3390/genes13010153 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Madar, László
Juhász, Lilla
Szűcs, Zsuzsanna
Kerkovits, Lóránt
Harangi, Mariann
Balogh, István
Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia
title Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia
title_full Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia
title_fullStr Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia
title_full_unstemmed Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia
title_short Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia
title_sort establishing the mutational spectrum of hungarian patients with familial hypercholesterolemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775528/
https://www.ncbi.nlm.nih.gov/pubmed/35052492
http://dx.doi.org/10.3390/genes13010153
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