Cargando…

Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family

Next-generation sequencing (NGS) is nowadays commonly used for clinical purposes, and represents an efficient approach for the molecular diagnosis of familial hypercholesterolemia (FH). Although the dominant form of the disease is mostly due to the low-density lipoprotein receptor (LDLR) small-scale...

Descripción completa

Detalles Bibliográficos
Autores principales: Concolino, Paola, De Paolis, Elisa, Moffa, Simona, Onori, Maria Elisabetta, Soldovieri, Laura, Ricciardi Tenore, Claudio, De Bonis, Maria, Rabacchi, Claudio, Santonocito, Concetta, Rinelli, Martina, Calandra, Sebastiano, Giaccari, Andrea, Urbani, Andrea, Minucci, Angelo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298720/
https://www.ncbi.nlm.nih.gov/pubmed/37372455
http://dx.doi.org/10.3390/genes14061275
_version_ 1785064187883421696
author Concolino, Paola
De Paolis, Elisa
Moffa, Simona
Onori, Maria Elisabetta
Soldovieri, Laura
Ricciardi Tenore, Claudio
De Bonis, Maria
Rabacchi, Claudio
Santonocito, Concetta
Rinelli, Martina
Calandra, Sebastiano
Giaccari, Andrea
Urbani, Andrea
Minucci, Angelo
author_facet Concolino, Paola
De Paolis, Elisa
Moffa, Simona
Onori, Maria Elisabetta
Soldovieri, Laura
Ricciardi Tenore, Claudio
De Bonis, Maria
Rabacchi, Claudio
Santonocito, Concetta
Rinelli, Martina
Calandra, Sebastiano
Giaccari, Andrea
Urbani, Andrea
Minucci, Angelo
author_sort Concolino, Paola
collection PubMed
description Next-generation sequencing (NGS) is nowadays commonly used for clinical purposes, and represents an efficient approach for the molecular diagnosis of familial hypercholesterolemia (FH). Although the dominant form of the disease is mostly due to the low-density lipoprotein receptor (LDLR) small-scale pathogenic variants, the copy number variations (CNVs) represent the underlying molecular defects in approximately 10% of FH cases. Here, we reported a novel large deletion in the LDLR gene involving exons 4–18, identified by the bioinformatic analysis of NGS data in an Italian family. A long PCR strategy was employed for the breakpoint region analysis where an insertion of six nucleotides (TTCACT) was found. Two Alu sequences, identified within intron 3 and exon 18, could underlie the identified rearrangement by a nonallelic homologous recombination (NAHR) mechanism. NGS proved to be an effective tool suitable for the identification of CNVs, together with small-scale alterations in the FH-related genes. For this purpose, the use and implementation of this cost-effective, efficient molecular approach meets the clinical need for personalized diagnosis in FH cases.
format Online
Article
Text
id pubmed-10298720
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102987202023-06-28 Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family Concolino, Paola De Paolis, Elisa Moffa, Simona Onori, Maria Elisabetta Soldovieri, Laura Ricciardi Tenore, Claudio De Bonis, Maria Rabacchi, Claudio Santonocito, Concetta Rinelli, Martina Calandra, Sebastiano Giaccari, Andrea Urbani, Andrea Minucci, Angelo Genes (Basel) Case Report Next-generation sequencing (NGS) is nowadays commonly used for clinical purposes, and represents an efficient approach for the molecular diagnosis of familial hypercholesterolemia (FH). Although the dominant form of the disease is mostly due to the low-density lipoprotein receptor (LDLR) small-scale pathogenic variants, the copy number variations (CNVs) represent the underlying molecular defects in approximately 10% of FH cases. Here, we reported a novel large deletion in the LDLR gene involving exons 4–18, identified by the bioinformatic analysis of NGS data in an Italian family. A long PCR strategy was employed for the breakpoint region analysis where an insertion of six nucleotides (TTCACT) was found. Two Alu sequences, identified within intron 3 and exon 18, could underlie the identified rearrangement by a nonallelic homologous recombination (NAHR) mechanism. NGS proved to be an effective tool suitable for the identification of CNVs, together with small-scale alterations in the FH-related genes. For this purpose, the use and implementation of this cost-effective, efficient molecular approach meets the clinical need for personalized diagnosis in FH cases. MDPI 2023-06-16 /pmc/articles/PMC10298720/ /pubmed/37372455 http://dx.doi.org/10.3390/genes14061275 Text en © 2023 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 Case Report
Concolino, Paola
De Paolis, Elisa
Moffa, Simona
Onori, Maria Elisabetta
Soldovieri, Laura
Ricciardi Tenore, Claudio
De Bonis, Maria
Rabacchi, Claudio
Santonocito, Concetta
Rinelli, Martina
Calandra, Sebastiano
Giaccari, Andrea
Urbani, Andrea
Minucci, Angelo
Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family
title Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family
title_full Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family
title_fullStr Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family
title_full_unstemmed Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family
title_short Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family
title_sort identification and molecular characterization of a novel large-scale variant (exons 4_18 loss) in the ldlr gene as a cause of familial hypercholesterolaemia in an italian family
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298720/
https://www.ncbi.nlm.nih.gov/pubmed/37372455
http://dx.doi.org/10.3390/genes14061275
work_keys_str_mv AT concolinopaola identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT depaoliselisa identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT moffasimona identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT onorimariaelisabetta identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT soldovierilaura identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT ricciarditenoreclaudio identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT debonismaria identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT rabacchiclaudio identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT santonocitoconcetta identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT rinellimartina identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT calandrasebastiano identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT giaccariandrea identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT urbaniandrea identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily
AT minucciangelo identificationandmolecularcharacterizationofanovellargescalevariantexons418lossintheldlrgeneasacauseoffamilialhypercholesterolaemiainanitalianfamily