Preprint Case Report Version 1 Preserved in Portico This version is not peer-reviewed

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

Paola Concolino
# ORCID logo ,
Elisa De Paolis
# ,
Simona Moffa
,
Maria Elisabetta Onori
ORCID logo ,
Laura Soldovieri
,
Claudio Ricciardi Tenore
,
Maria De Bonis
,
Claudio Rabacchi
,
Concetta Santonocito
,
Martina Rinelli
,
Sebastiano Calandra
,
Andrea Giaccari
,
Andrea Urbani
* ,
Angelo Minucci
* ORCID logo
#
These authors contributed equally to the work.
Version 1 : Received: 27 May 2023 / Approved: 30 May 2023 / Online: 30 May 2023 (04:25:02 CEST)

A peer-reviewed article of this Preprint also exists.

Concolino, P.; De Paolis, E.; Moffa, S.; Onori, M.E.; Soldovieri, L.; Ricciardi Tenore, C.; De Bonis, M.; Rabacchi, C.; Santonocito, C.; Rinelli, M.; Calandra, S.; Giaccari, A.; Urbani, A.; Minucci, A. 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. Genes 2023, 14, 1275. Concolino, P.; De Paolis, E.; Moffa, S.; Onori, M.E.; Soldovieri, L.; Ricciardi Tenore, C.; De Bonis, M.; Rabacchi, C.; Santonocito, C.; Rinelli, M.; Calandra, S.; Giaccari, A.; Urbani, A.; Minucci, A. 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. Genes 2023, 14, 1275.

Abstract

Next Generation Sequencing (NGS), now widely used in the clinical setting, offers an efficient and comprehensive molecular approach for patients with Familial hypercholesterolemia (FH). Although the dominant form of disease is mostly due to low-density lipoprotein receptor (LDLR) small-scale pathogenic variants, approximately 10% of molecularly defined FH cases are due to Copy Number Variations (CNVs). Here, we report a novel large deletion of the LDLR gene involving exons 4–18, identified by bioinformatic analysis of NGS data in an Italian family. A long PCR strategy was employed for breakpoint region analysis where an insertion of 6 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 proves to be a powerful tool used to precisely identify CNVs, in addition to small-scale variants in FH-related genes. At this purpose, the use and implementation of this cost-effective, efficient molecular approach meets the clinical need for personalized diagnosis in FH cases.

Keywords

Familial hypercholesterolemia; Next Generation Sequencing; LDL-cholesterol; LDLR gene; Copy number variations (CNVs); Alu sequences

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.