Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing.
familial hypercholesterolemia
genetic study
low-density lipoprotein cholesterol
monogenic
registry
whole-genome sequencing
Journal
Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588
Informations de publication
Date de publication:
07 Aug 2023
07 Aug 2023
Historique:
received:
28
06
2023
revised:
14
07
2023
accepted:
01
08
2023
medline:
12
8
2023
pubmed:
12
8
2023
entrez:
12
8
2023
Statut:
epublish
Résumé
There is limited data on the genetic characteristics of patients with familial hypercholesterolemia (FH) in Latvia. We aim to describe monogenic variants in patients from the Latvian Registry of FH (LRFH). Whole genome sequencing with 30× coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 ± 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol ≥6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the Despite the high clinical likelihood of FH, confirmed P/LP variants were detected in only 20.9% of patients in the Latvian cohort when assessed with genome-wide next generation sequencing.
Sections du résumé
BACKGROUND
BACKGROUND
There is limited data on the genetic characteristics of patients with familial hypercholesterolemia (FH) in Latvia. We aim to describe monogenic variants in patients from the Latvian Registry of FH (LRFH).
METHODS
METHODS
Whole genome sequencing with 30× coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population.
RESULTS
RESULTS
Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 ± 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol ≥6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the
CONCLUSIONS
CONCLUSIONS
Despite the high clinical likelihood of FH, confirmed P/LP variants were detected in only 20.9% of patients in the Latvian cohort when assessed with genome-wide next generation sequencing.
Identifiants
pubmed: 37568561
pii: jcm12155160
doi: 10.3390/jcm12155160
pmc: PMC10419451
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Latvian Council of Science
ID : lzp-2020/1-0151
Références
Lancet. 2013 Apr 13;381(9874):1293-301
pubmed: 23433573
Bioinformatics. 2012 Oct 15;28(20):2678-9
pubmed: 22914218
Gigascience. 2021 Feb 16;10(2):
pubmed: 33590861
Genet Med. 2018 Jun;20(6):591-598
pubmed: 29261184
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Front Genet. 2020 Dec 02;11:592588
pubmed: 33343633
Curr Opin Lipidol. 2015 Apr;26(2):103-13
pubmed: 25692347
Curr Opin Lipidol. 2019 Apr;30(2):63-70
pubmed: 30664016
J Biomed Sci. 2016 Apr 16;23:39
pubmed: 27084339
Atherosclerosis. 2016 Oct;253:88-93
pubmed: 27596133
Nat Commun. 2018 Aug 23;9(1):3391
pubmed: 30140000
Front Genet. 2022 Feb 28;13:849008
pubmed: 35295947
Genet Med. 2022 Feb;24(2):293-306
pubmed: 34906454
Atherosclerosis. 2015 Nov;243(1):257-9
pubmed: 26408930
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Eur Heart J. 2021 Sep 7;42(34):3227-3337
pubmed: 34458905
J Med Genet. 2014 Aug;51(8):537-44
pubmed: 24987033
Eur Heart J. 2013 Dec;34(45):3478-90a
pubmed: 23956253
Hum Mutat. 2018 Nov;39(11):1631-1640
pubmed: 30311388
Atherosclerosis. 2005 May;180(1):155-60
pubmed: 15823288
J Epidemiol. 2018 Aug 5;28(8):353-360
pubmed: 29576601
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
J Lipid Res. 2021;62:100139
pubmed: 34666015
J Am Heart Assoc. 2021 May 4;10(9):e018932
pubmed: 33890476
PLoS One. 2017 May 11;12(5):e0177459
pubmed: 28494014
J Clin Lipidol. 2017 Mar - Apr;11(2):477-484.e2
pubmed: 28502505
J Am Coll Cardiol. 2018 Aug 7;72(6):662-680
pubmed: 30071997
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Eur Heart J. 2016 May 01;37(17):1384-94
pubmed: 26908947
Clin Genet. 2018 Jul;94(1):132-140
pubmed: 29572815
Circ Genom Precis Med. 2022 Jun;15(3):e003390
pubmed: 35549507
Atherosclerosis. 2018 Oct;277:347-354
pubmed: 30270070
J Am Coll Cardiol. 2019 Jul 30;74(4):512-522
pubmed: 31345425
J Am Heart Assoc. 2022 Apr 5;11(7):e023668
pubmed: 35322671
Eur Heart J. 2017 Feb 21;38(8):574-576
pubmed: 27161618
J Am Coll Cardiol. 2016 Jun 7;67(22):2578-89
pubmed: 27050191