| Title: |
Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia |
| Authors: |
Rimbert, Antoine; Pichelin, Matthieu; Lecointe, Simon; Marrec, Marie; Le Scouarnec, Solena; Barrak, Elias; Croyal, Mikael; Krempf, Michel; Le Marec, Hervé; Redon, Richard; Schott, Jean-Jacques; Magré, Jocelyne; Cariou, Bertrand |
| Contributors: |
ITX - unité de recherche de l'institut du thorax (ITX); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Physiopathologie des Adaptations Nutritionnelles (PhAN); Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Fondation Leducq-13CVD03 / Fundazione Cariplo 2012-0549 /Fondation de France 2015-00047967 |
| Source: |
ISSN: 0021-9150. |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2016 |
| Collection: |
Université de Nantes: HAL-UNIV-NANTES |
| Subject Terms: |
Target next generation sequencing; Familial hypobetalipoproteinemia; APOB; Molecular diagnosis; PCSK9; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; BACKGROUND AND AIMS: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by decreased plasma levels of LDL-cholesterol and apolipoprotein B (ApoB). Currently, genetic diagnosis in FHBL relies largely on Sanger sequencing to identify APOB and PCSK9 gene mutations and on western blotting to detect truncated ApoB species. METHODS: Here, we applied targeted enrichment and next-generation sequencing (NGS) on a panel of three FHBL genes and two abetalipoproteinemia genes (APOB, PCSK9, ANGPTL3, MTTP and SAR1B). RESULTS: In this study, we identified five likely pathogenic heterozygous rare variants. These include four novel nonsense mutations in APOB (p.Gln845*, p.Gln2571*, p.Cys2933* and p.Ser3718*) and a rare variant in PCSK9 (Minor Allele Frequency \textless0.1%). The affected family members tested were shown to be carriers, suggesting co-segregation with low LDL-C. CONCLUSIONS: Our study further demonstrates that NGS is a reliable and practical approach for the molecular screening of FHBL-causative genes that may provide a mean for deciphering the genetic basis in FHBL. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/27179706; PRODINRA: 375418; PUBMED: 27179706; WOS: 000377982800008 |
| DOI: |
10.1016/j.atherosclerosis.2016.04.010 |
| Availability: |
https://hal.science/hal-01831745; https://hal.science/hal-01831745v1/document; https://hal.science/hal-01831745v1/file/1-s2.0-S0021915016301411-main.pdf; https://doi.org/10.1016/j.atherosclerosis.2016.04.010 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.7413ADCD |
| Database: |
BASE |