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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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 |
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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 |
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