Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)

The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype)...

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Autores principales:	Elena Shakhtshneider, Dinara Ivanoshchuk, Olga Timoshchenko, Pavel Orlov, Sergey Semaev, Emil Valeev, Andrew Goonko, Nataliya Ladygina, Mikhail Voevoda
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	familial hypercholesterolemia targeted sequencing technologies multiplex ligation-dependent probe amplification <i>LDLR</i> <i>APOB</i> <i>ABCG5</i> Medicine R
Acceso en línea:	https://doaj.org/article/7e91683224bd4fd59502263c6c0c43ec
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spelling	oai:doaj.org-article:7e91683224bd4fd59502263c6c0c43ec2021-11-25T18:08:12ZAnalysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)10.3390/jpm111112322075-4426https://doaj.org/article/7e91683224bd4fd59502263c6c0c43ec2021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1232https://doaj.org/toc/2075-4426The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype). For patients without functionally significant substitutions in the above genes, multiplex ligation-dependent probe amplification was conducted to determine bigger mutations (deletions and/or duplications) in the <i>LDLR</i> promoter and exons. A clinically significant variant in some gene associated with familial hypercholesterolemia was identified in 47.5% of the subjects. Clinically significant variants in the <i>LDLR</i> gene were identified in 19 probands (73.1% of all variants identified in probands); in three probands (11.5%), pathogenic variants were found in the <i>APOB</i> gene; and in four probands (15.4%), rare, clinically significant variants were identified in genes <i>LPL</i>, <i>SREBF1</i>, <i>APOC3</i>, and <i>ABCG5</i>. In 12 (85.7%) of 14 children of the probands, clinically significant variants were detectable in genes associated with familial hypercholesterolemia. The use of clinical criteria, targeted sequencing, and multiplex ligation-dependent probe amplification makes it possible to identify carriers of rare clinically significant variants in a wide range of lipid metabolism genes and to investigate their influence on phenotypic manifestations of familial hypercholesterolemia.Elena ShakhtshneiderDinara IvanoshchukOlga TimoshchenkoPavel OrlovSergey SemaevEmil ValeevAndrew GoonkoNataliya LadyginaMikhail VoevodaMDPI AGarticlefamilial hypercholesterolemiatargeted sequencing technologiesmultiplex ligation-dependent probe amplification<i>LDLR</i><i>APOB</i><i>ABCG5</i>MedicineRENJournal of Personalized Medicine, Vol 11, Iss 1232, p 1232 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	familial hypercholesterolemia targeted sequencing technologies multiplex ligation-dependent probe amplification <i>LDLR</i> <i>APOB</i> <i>ABCG5</i> Medicine R
spellingShingle	familial hypercholesterolemia targeted sequencing technologies multiplex ligation-dependent probe amplification <i>LDLR</i> <i>APOB</i> <i>ABCG5</i> Medicine R Elena Shakhtshneider Dinara Ivanoshchuk Olga Timoshchenko Pavel Orlov Sergey Semaev Emil Valeev Andrew Goonko Nataliya Ladygina Mikhail Voevoda Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)
description	The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype). For patients without functionally significant substitutions in the above genes, multiplex ligation-dependent probe amplification was conducted to determine bigger mutations (deletions and/or duplications) in the <i>LDLR</i> promoter and exons. A clinically significant variant in some gene associated with familial hypercholesterolemia was identified in 47.5% of the subjects. Clinically significant variants in the <i>LDLR</i> gene were identified in 19 probands (73.1% of all variants identified in probands); in three probands (11.5%), pathogenic variants were found in the <i>APOB</i> gene; and in four probands (15.4%), rare, clinically significant variants were identified in genes <i>LPL</i>, <i>SREBF1</i>, <i>APOC3</i>, and <i>ABCG5</i>. In 12 (85.7%) of 14 children of the probands, clinically significant variants were detectable in genes associated with familial hypercholesterolemia. The use of clinical criteria, targeted sequencing, and multiplex ligation-dependent probe amplification makes it possible to identify carriers of rare clinically significant variants in a wide range of lipid metabolism genes and to investigate their influence on phenotypic manifestations of familial hypercholesterolemia.
format	article
author	Elena Shakhtshneider Dinara Ivanoshchuk Olga Timoshchenko Pavel Orlov Sergey Semaev Emil Valeev Andrew Goonko Nataliya Ladygina Mikhail Voevoda
author_facet	Elena Shakhtshneider Dinara Ivanoshchuk Olga Timoshchenko Pavel Orlov Sergey Semaev Emil Valeev Andrew Goonko Nataliya Ladygina Mikhail Voevoda
author_sort	Elena Shakhtshneider
title	Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)
title_short	Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)
title_full	Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)
title_fullStr	Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)
title_full_unstemmed	Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)
title_sort	analysis of rare variants in genes related to lipid metabolism in patients with familial hypercholesterolemia in western siberia (russia)
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7e91683224bd4fd59502263c6c0c43ec
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Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)

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