Genetic variants identified by target next-generation sequencing in heart transplant patients with dilated cardiomyopathy
Rev Port Cardiol (Engl Ed). 2019 Jun;38(6):441-447.
doi: 10.1016/j.repc.2019.02.006.
Epub 2019 Jul 11.
[Article in
English,
Portuguese]
Authors
Elisabete Martins
1
, Alexandra Sousa
2
, Paulo Canedo
3
, Sérgio Leite
4
, Roberto Pinto
5
, Manuel Campelo
6
, Sandra Amorim
7
, Brenda Moura
8
, José Manuel Lopes
9
, José Carlos Machado
10
, José Silva Cardoso
6
; FATIMA investigators
Affiliations
- 1 Department of Medicine, Faculty of Medicine, University of Porto, Portugal; Institute for Innovation and Health Research (I3S), Porto, Portugal; Department of Cardiology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal. Electronic address: elisabetemartins09@gmail.com.
- 2 Department of Medicine, Faculty of Medicine, University of Porto, Portugal; Center for Research in Health Technologies and Services (Cintesis), Porto, Portugal; Department of Cardiology, Santa Maria Maior Hospital, Barcelos, Portugal.
- 3 Institute for Innovation and Health Research (I3S), Porto, Portugal.
- 4 Department of Medicine, Faculty of Medicine, University of Porto, Portugal.
- 5 Department of Cardiology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal.
- 6 Department of Medicine, Faculty of Medicine, University of Porto, Portugal; Center for Research in Health Technologies and Services (Cintesis), Porto, Portugal; Department of Cardiology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal.
- 7 Center for Research in Health Technologies and Services (Cintesis), Porto, Portugal; Department of Cardiology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal.
- 8 Hospital das Forças Armadas, Porto, Portugal.
- 9 Institute for Innovation and Health Research (I3S), Porto, Portugal; Department of Pathology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal; Departament de Pathology and Oncology, Faculty of Medicine, Porto, Portugal.
- 10 Department of Medicine, Faculty of Medicine, University of Porto, Portugal; Institute for Innovation and Health Research (I3S), Porto, Portugal.
Abstract
Introduction and objectives:
Dilated cardiomyopathy (DCM) is a myocardial disease that can progress to a terminal stage, requiring heart transplantation. In this work we aim to contribute to knowledge of genetic variants in adult patients undergoing heart transplantation due to end-stage DCM, reporting the results obtained in our single-center tertiary hospital series using target next-generation sequencing (NGS).
Methods and results:
Genetic variants were screened in 15 genes, preselected based on variants previously identified in DCM patients. Thirteen unrelated patients were included, nine (69%) male, mean age at diagnosis 33±13 years, eight (62%) with familial DCM. Nine genetic variants were identified in six (46%) patients: five in LMNA, two in LBD3, one in TNNT2 and one in TCAP. These variants were new in most patients. The majority were classified as of uncertain significance. Two patients were double and triple heterozygotes in the LBD3 and LMNA genes, respectively.
Conclusion:
Our results highlight the potential of NGS in the genetic characterization of DCM patients. LMNA is one of the most frequently mutated genes and should be included in all target gene assessments of end-stage DCM patients until more data are available.
Keywords:
Dilated cardiomyopathy; Genetic variants; Heart transplantation; Miocardiopatia dilatada; Next-generation sequencing; Sequenciação de nova geração; Transplante cardíaco; Variantes genéticas.
Copyright © 2019 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.
MeSH terms
-
Adult
-
Cardiomyopathy, Dilated / genetics*
-
Cardiomyopathy, Dilated / surgery
-
DNA / genetics*
-
DNA Mutational Analysis
-
Female
-
Follow-Up Studies
-
Genetic Variation
-
Heart Transplantation*
-
High-Throughput Nucleotide Sequencing
-
Humans
-
Lamin Type A / genetics*
-
Lamin Type A / metabolism
-
Male
-
Middle Aged
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Mutation*
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Phenotype
Substances
-
LMNA protein, human
-
Lamin Type A
-
DNA