TY - JOUR
T1 - Identification of two novel LDLR variants by next generation sequencing
AU - Moffa, Simona
AU - Mazzuccato, Giorgia
AU - de Bonis, Maria
AU - de Paolis, Elisa
AU - Onori, Maria Elisabetta
AU - Pontecorvi, Alfredo
AU - Urbani, Andrea
AU - Giaccari, Andrea
AU - Capoluongo, Ettore
AU - Minucci, Angelo
N1 - Funding Information:
We would like to thank Franziska M. Lohmeyer for critically reviewing and editing our manuscript.
Publisher Copyright:
© 2020 Istituto Superiore di Sanita. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Introduction. Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C). Targeted Next Generation Sequencing (NGS) is a new opportunity to expand the existing pathogenic variants (PVs) spectrum associated to FH. Our aim was to report a diagnostic NGS-based approach to detect variants associated to FH. Methods. We report two patients: a 48-year-old Asian woman, without known history of hypercholesterolemia and a 46-year-old Caucasian man, with childhood hypercholesterolemia. Results. An effective NGS-based pipeline, FH-Devyser kit/Amplicon Suite, beginning from sequencing to data analysis, did not identify known PVs in the LDLR, APOB, APOE, LDLRAP1, STAP1 and PCSK9 genes, but revealed two novel LDLR variants (c.1564A>T, p.Ile522Phe and c.1688C>T, p.Pro563Leu). Discussion and conclusions. This study showed that an effective NGS-based pipeline led to a definitive diagnosis in two FH families, allowing to plan their therapeutic treatment. Although the functional consequence of the two LDLR variants needs to be assessed in vitro, the in silico analysis and high preservation of the two amino acid positions observed in the LDLR protein, across different animal species, suggest that both variants are deleterious.
AB - Introduction. Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C). Targeted Next Generation Sequencing (NGS) is a new opportunity to expand the existing pathogenic variants (PVs) spectrum associated to FH. Our aim was to report a diagnostic NGS-based approach to detect variants associated to FH. Methods. We report two patients: a 48-year-old Asian woman, without known history of hypercholesterolemia and a 46-year-old Caucasian man, with childhood hypercholesterolemia. Results. An effective NGS-based pipeline, FH-Devyser kit/Amplicon Suite, beginning from sequencing to data analysis, did not identify known PVs in the LDLR, APOB, APOE, LDLRAP1, STAP1 and PCSK9 genes, but revealed two novel LDLR variants (c.1564A>T, p.Ile522Phe and c.1688C>T, p.Pro563Leu). Discussion and conclusions. This study showed that an effective NGS-based pipeline led to a definitive diagnosis in two FH families, allowing to plan their therapeutic treatment. Although the functional consequence of the two LDLR variants needs to be assessed in vitro, the in silico analysis and high preservation of the two amino acid positions observed in the LDLR protein, across different animal species, suggest that both variants are deleterious.
KW - FH-Devyser Kit
KW - LDL-cholesterol
KW - Next generation sequencing
KW - Novel LDLR variants
KW - SmartSeq
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U2 - 10.4415/ANN_20_01_17
DO - 10.4415/ANN_20_01_17
M3 - Article
C2 - 32242544
AN - SCOPUS:85082980209
VL - 56
SP - 122
EP - 127
JO - Annali dell'Istituto Superiore di Sanita
JF - Annali dell'Istituto Superiore di Sanita
SN - 0021-2571
IS - 1
ER -