A novel low-density lipoprotein receptor variant in a Ukrainian patient: a case report and overview of the disease-causing low-density lipoprotein receptor variants associated to familial hypercholesterolemia.
FH-Devyser Kit
Familial hypercholesterolemia
LDL-cholesterol
Next generation sequencing
Novel LDLR variant
Ukrainian population
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
26
08
2021
accepted:
24
11
2021
pubmed:
1
12
2021
medline:
29
3
2022
entrez:
30
11
2021
Statut:
ppublish
Résumé
Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein-cholesterol levels and it is primarily caused by pathogenic/likely pathogenic variants (P/LPVs) in LDLR, APOB or PCSK9 genes. Next generation sequencing (NGS) technology allows the evaluation of more genes simultaneously, rising the diagnostic throughput of genomics laboratories. We report a Ukrainian 37-year-old woman hypercholesterolemic since 2010. Despite a suggestive family history, FH was suspected only when the patient referred to the Endocrine and Metabolic Diseases Center of the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. After specialist advice, genetic testing was offered to the patient at our Molecular and Genomic Diagnostics Unit. A targeted NGS-based pipeline highlighted a novel out-of-frame deletion in the LDLR gene. This variant has a clear deleterious effect on the LDLR protein and it can be classified as PV. The ideal model of care for FH is an evidence-based system aimed to provide the highest-quality health services to all FH patients. In fact, this study reports that the integrated care pathway adopted in our hospital for FH patients led successfully to the discovery of a novel LDLR PV in an Ukrainian patient. The finding of this LDLR variant allowed the clinical FH diagnosis in this patient and in her family, expanding the knowledge of FH-related genetic variants in the Ukrainian population.
Sections du résumé
BACKGROUND
BACKGROUND
Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein-cholesterol levels and it is primarily caused by pathogenic/likely pathogenic variants (P/LPVs) in LDLR, APOB or PCSK9 genes. Next generation sequencing (NGS) technology allows the evaluation of more genes simultaneously, rising the diagnostic throughput of genomics laboratories.
MATERIALS AND METHODS
METHODS
We report a Ukrainian 37-year-old woman hypercholesterolemic since 2010. Despite a suggestive family history, FH was suspected only when the patient referred to the Endocrine and Metabolic Diseases Center of the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. After specialist advice, genetic testing was offered to the patient at our Molecular and Genomic Diagnostics Unit.
RESULTS
RESULTS
A targeted NGS-based pipeline highlighted a novel out-of-frame deletion in the LDLR gene. This variant has a clear deleterious effect on the LDLR protein and it can be classified as PV.
CONCLUSIONS
CONCLUSIONS
The ideal model of care for FH is an evidence-based system aimed to provide the highest-quality health services to all FH patients. In fact, this study reports that the integrated care pathway adopted in our hospital for FH patients led successfully to the discovery of a novel LDLR PV in an Ukrainian patient. The finding of this LDLR variant allowed the clinical FH diagnosis in this patient and in her family, expanding the knowledge of FH-related genetic variants in the Ukrainian population.
Identifiants
pubmed: 34846648
doi: 10.1007/s11033-021-07015-3
pii: 10.1007/s11033-021-07015-3
doi:
Substances chimiques
Cholesterol, LDL
0
LDLR protein, human
0
Receptors, LDL
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1623-1630Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.
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