Genetic heterogeneity of cardiomyopathy and its correlation with patient care.
Cardiomyopathy
Genotype
Prognosis
Whole-exome sequencing
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
30 10 2023
30 10 2023
Historique:
received:
28
01
2023
accepted:
21
08
2023
medline:
2
11
2023
pubmed:
31
10
2023
entrez:
31
10
2023
Statut:
epublish
Résumé
Cardiomyopathy, which is a genetically and phenotypically heterogeneous pathological condition, is associated with increased morbidity and mortality. Genetic diagnosis of cardiomyopathy enables accurate phenotypic classification and optimum patient management and counseling. This study investigated the genetic spectrum of cardiomyopathy and its correlation with the clinical course of the disease. The samples of 72 Korean patients with cardiomyopathy (43 males and 29 females) were subjected to whole-exome sequencing (WES). The familial information and clinical characteristics of the patients were reviewed and analyzed according to their genotypes. Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy was detected in 41 (56.9%), 25 (34.7%), 4 (5.6%), and 2 (2.8%) patients, respectively. WES analysis revealed positive results in 37 (51.4%) patients. Subsequent familial testing identified ten additional familial cases. Among DCM cases, 19 (46.3%) patients exhibited positive results, with TTN variants being the most common alteration, followed by LMNA and MYH7 variants. Meanwhile, among HCM cases, 15 (60%) patients exhibited positive results with MYH7 variants being the most common alteration. In six patients with positive results, extracardiac surveillance was warranted based on disease information. The incidence of worse outcomes, such as mortality and life-threatening arrhythmic events, in patients with DCM harboring LMNA variants, was higher than that in patients with DCM harboring TTN or MYH7 variants. Diverse genotypes were identified in a substantial proportion of patients with cardiomyopathy. Genetic diagnosis enables personalized disease surveillance and management.
Sections du résumé
BACKGROUND
Cardiomyopathy, which is a genetically and phenotypically heterogeneous pathological condition, is associated with increased morbidity and mortality. Genetic diagnosis of cardiomyopathy enables accurate phenotypic classification and optimum patient management and counseling. This study investigated the genetic spectrum of cardiomyopathy and its correlation with the clinical course of the disease.
METHODS
The samples of 72 Korean patients with cardiomyopathy (43 males and 29 females) were subjected to whole-exome sequencing (WES). The familial information and clinical characteristics of the patients were reviewed and analyzed according to their genotypes.
RESULTS
Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy was detected in 41 (56.9%), 25 (34.7%), 4 (5.6%), and 2 (2.8%) patients, respectively. WES analysis revealed positive results in 37 (51.4%) patients. Subsequent familial testing identified ten additional familial cases. Among DCM cases, 19 (46.3%) patients exhibited positive results, with TTN variants being the most common alteration, followed by LMNA and MYH7 variants. Meanwhile, among HCM cases, 15 (60%) patients exhibited positive results with MYH7 variants being the most common alteration. In six patients with positive results, extracardiac surveillance was warranted based on disease information. The incidence of worse outcomes, such as mortality and life-threatening arrhythmic events, in patients with DCM harboring LMNA variants, was higher than that in patients with DCM harboring TTN or MYH7 variants.
CONCLUSIONS
Diverse genotypes were identified in a substantial proportion of patients with cardiomyopathy. Genetic diagnosis enables personalized disease surveillance and management.
Identifiants
pubmed: 37904158
doi: 10.1186/s12920-023-01639-z
pii: 10.1186/s12920-023-01639-z
pmc: PMC10614404
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
270Informations de copyright
© 2023. The Author(s).
Références
J Am Coll Cardiol. 2007 Dec 18;50(25):2399-403
pubmed: 18154965
Circulation. 2006 Apr 11;113(14):1807-16
pubmed: 16567565
J Am Coll Cardiol. 2003 Mar 5;41(5):771-80
pubmed: 12628721
Genet Med. 2017 Feb;19(2):192-203
pubmed: 27532257
J Clin Invest. 2013 Jan;123(1):19-26
pubmed: 23281406
PLoS One. 2017 Aug 3;12(8):e0181465
pubmed: 28771489
Clin Genet. 2020 Dec;98(6):562-570
pubmed: 32901917
Circ Cardiovasc Genet. 2010 Aug;3(4):314-22
pubmed: 20716751
Genet Med. 2015 Jul;17(7):587-95
pubmed: 25394171
J Am Coll Cardiol. 2011 Apr 19;57(16):1641-9
pubmed: 21492761
Circ Cardiovasc Genet. 2012 Aug 1;5(4):391-9
pubmed: 22763267
Genet Med. 2014 Aug;16(8):601-8
pubmed: 24503780
JAMA Cardiol. 2018 Apr 1;3(4):341-345
pubmed: 29490334
N Engl J Med. 2014 Sep 18;371(12):1170
pubmed: 25229935
Genet Med. 2013 Jul;15(7):565-74
pubmed: 23788249
Am J Cardiol. 2014 Sep 1;114(5):769-76
pubmed: 25037680
N Engl J Med. 2000 Dec 7;343(23):1688-96
pubmed: 11106718
Nat Genet. 2017 Jan;49(1):46-53
pubmed: 27869827
Eur Heart J. 2008 Jan;29(2):270-6
pubmed: 17916581
J Am Coll Cardiol. 2009 Jul 14;54(3):201-11
pubmed: 19589432
Biomed Res Int. 2015;2015:561819
pubmed: 26199943
Eur Heart J. 2015 Nov 1;36(41):2793-2867
pubmed: 26320108
Biochem Res Int. 2012;2012:796926
pubmed: 22924131
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Heart. 2002 Feb;87(2):126-30
pubmed: 11796547
J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239
pubmed: 23747642
Genet Med. 2018 Sep;20(9):899-909
pubmed: 29904160
NPJ Genom Med. 2018 Jul 9;3:16
pubmed: 30002876
J Am Coll Cardiol. 2005 Apr 5;45(7):969-81
pubmed: 15808750
Genes (Basel). 2020 Nov 16;11(11):
pubmed: 33207664
J Am Coll Cardiol. 2016 Dec 27;68(25):2871-2886
pubmed: 28007147
Eur Heart J. 2015 May 7;36(18):1123-35a
pubmed: 25163546
J Card Fail. 2012 May;18(5):396-403
pubmed: 22555271
Circ J. 2013;77(2):462-9
pubmed: 23095684
Genet Med. 2015 Nov;17(11):880-8
pubmed: 25611685
Am J Cardiol. 2011 Oct 15;108(8):1171-6
pubmed: 21798502
Sci Rep. 2018 Jan 31;8(1):1998
pubmed: 29386531
Eur Heart J. 2016 Jun 14;37(23):1850-8
pubmed: 26792875