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Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia

BACKGROUND: Lecithin:cholesterol acyltransferase (LCAT) is responsible for cholesterol esterification in plasma. Mutations of LCAT gene cause familial LCAT deficiency, a metabolic disorder characterized by hypoalphalipoproteinemia. Apolipoprotein B (apoB) is the main protein component of very-low-de...

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Autores principales: Conca, Paola, Pileggi, Silvana, Simonelli, Sara, Boer, Emanuela, Boscutti, Giuliano, Magnolo, Lucia, Tarugi, Patrizia, Penco, Silvana, Franceschini, Guido, Calabresi, Laura, Gomaraschi, Monica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361081/
https://www.ncbi.nlm.nih.gov/pubmed/22658148
http://dx.doi.org/10.1016/j.jacl.2012.01.006
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author Conca, Paola
Pileggi, Silvana
Simonelli, Sara
Boer, Emanuela
Boscutti, Giuliano
Magnolo, Lucia
Tarugi, Patrizia
Penco, Silvana
Franceschini, Guido
Calabresi, Laura
Gomaraschi, Monica
author_facet Conca, Paola
Pileggi, Silvana
Simonelli, Sara
Boer, Emanuela
Boscutti, Giuliano
Magnolo, Lucia
Tarugi, Patrizia
Penco, Silvana
Franceschini, Guido
Calabresi, Laura
Gomaraschi, Monica
author_sort Conca, Paola
collection PubMed
description BACKGROUND: Lecithin:cholesterol acyltransferase (LCAT) is responsible for cholesterol esterification in plasma. Mutations of LCAT gene cause familial LCAT deficiency, a metabolic disorder characterized by hypoalphalipoproteinemia. Apolipoprotein B (apoB) is the main protein component of very-low-density lipoproteins and low-density lipoprotein (LDL). Mutations of APOB gene cause familial hypobetalipoproteinemia, a codominant disorder characterized by low plasma levels of LDL cholesterol and apoB. OBJECTIVE: This was a genetic and biochemical analysis of an Italian kindred with hypobetalipoproteinemia whose proband presented with hypoalphalipoproteinemia and severe chronic kidney disease. METHODS: Plasma lipids and apolipoproteins, cholesterol esterification, and high-density lipoprotein (HDL) subclass distribution were analyzed. LCAT and APOB genes were sequenced. RESULTS: The proband had severe impairment of plasma cholesterol esterification and high preβ-HDL content. He was heterozygote for the novel LCAT P406L variant, as were two other family members. The proband’s wife and children presented with familial hypobetalipoproteinemia and were heterozygotes for the novel apoB H1401R variant. Cholesterol esterification rate of apoB H1401R carriers was reduced, likely attributable to the low amount of circulating LDL. After renal transplantation, proband’s lipid profile, HDL subclass distribution, and plasma cholesterol esterification were almost at normal levels, suggesting a mild contribution of the LCAT P406L variant to his pretransplantation severe hypoalphalipoproteinemia and impairment of plasma cholesterol esterification. CONCLUSION: LCAT P406L variant had a mild effect on lipid profile, HDL subclass distribution, and plasma cholesterol esterification. ApoB H1401R variant was identified as possible cause of familial hypobetalipoproteinemia and resulted in a reduction of cholesterol esterification rate.
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spelling pubmed-33610812012-05-31 Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia Conca, Paola Pileggi, Silvana Simonelli, Sara Boer, Emanuela Boscutti, Giuliano Magnolo, Lucia Tarugi, Patrizia Penco, Silvana Franceschini, Guido Calabresi, Laura Gomaraschi, Monica J Clin Lipidol Original Article BACKGROUND: Lecithin:cholesterol acyltransferase (LCAT) is responsible for cholesterol esterification in plasma. Mutations of LCAT gene cause familial LCAT deficiency, a metabolic disorder characterized by hypoalphalipoproteinemia. Apolipoprotein B (apoB) is the main protein component of very-low-density lipoproteins and low-density lipoprotein (LDL). Mutations of APOB gene cause familial hypobetalipoproteinemia, a codominant disorder characterized by low plasma levels of LDL cholesterol and apoB. OBJECTIVE: This was a genetic and biochemical analysis of an Italian kindred with hypobetalipoproteinemia whose proband presented with hypoalphalipoproteinemia and severe chronic kidney disease. METHODS: Plasma lipids and apolipoproteins, cholesterol esterification, and high-density lipoprotein (HDL) subclass distribution were analyzed. LCAT and APOB genes were sequenced. RESULTS: The proband had severe impairment of plasma cholesterol esterification and high preβ-HDL content. He was heterozygote for the novel LCAT P406L variant, as were two other family members. The proband’s wife and children presented with familial hypobetalipoproteinemia and were heterozygotes for the novel apoB H1401R variant. Cholesterol esterification rate of apoB H1401R carriers was reduced, likely attributable to the low amount of circulating LDL. After renal transplantation, proband’s lipid profile, HDL subclass distribution, and plasma cholesterol esterification were almost at normal levels, suggesting a mild contribution of the LCAT P406L variant to his pretransplantation severe hypoalphalipoproteinemia and impairment of plasma cholesterol esterification. CONCLUSION: LCAT P406L variant had a mild effect on lipid profile, HDL subclass distribution, and plasma cholesterol esterification. ApoB H1401R variant was identified as possible cause of familial hypobetalipoproteinemia and resulted in a reduction of cholesterol esterification rate. Elsevier 2012-05 /pmc/articles/PMC3361081/ /pubmed/22658148 http://dx.doi.org/10.1016/j.jacl.2012.01.006 Text en © 2012 Elsevier Inc. https://creativecommons.org/licenses/by/4.0/ Open Access under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) license
spellingShingle Original Article
Conca, Paola
Pileggi, Silvana
Simonelli, Sara
Boer, Emanuela
Boscutti, Giuliano
Magnolo, Lucia
Tarugi, Patrizia
Penco, Silvana
Franceschini, Guido
Calabresi, Laura
Gomaraschi, Monica
Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia
title Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia
title_full Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia
title_fullStr Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia
title_full_unstemmed Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia
title_short Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia
title_sort novel missense variants in lcat and apob genes in an italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361081/
https://www.ncbi.nlm.nih.gov/pubmed/22658148
http://dx.doi.org/10.1016/j.jacl.2012.01.006
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