Phenotype/Genotype Relationship in Left Ventricular Noncompaction: Ion Channel Gene Mutations Are Associated With Preserved Left Ventricular Systolic Function and Biventricular Noncompaction: Phenotype/Genotype of Noncompaction.
Genotype
Heart Failure
Humans
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
/ genetics
Ion Channels
Isolated Noncompaction of the Ventricular Myocardium
/ diagnostic imaging
Muscle Proteins
/ genetics
Mutation
Phenotype
Potassium Channels
/ genetics
Ryanodine Receptor Calcium Release Channel
/ genetics
Ventricular Function, Left
Left ventricular noncompaction
echocardiography
genotype
phenotype
registry
Journal
Journal of cardiac failure
ISSN: 1532-8414
Titre abrégé: J Card Fail
Pays: United States
ID NLM: 9442138
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
06
08
2020
revised:
16
01
2021
accepted:
17
01
2021
entrez:
5
6
2021
pubmed:
6
6
2021
medline:
21
10
2021
Statut:
ppublish
Résumé
Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC). From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18.5%; P < .001) than the 81 other patients with LVNC. Among them, both the 19 patients with an HCN4 mutation and the 11 patients with an RYR2 mutation presented with a higher LV ejection fraction and more frequent biventricular noncompaction than the 81 patients with LVNC but with no mutation in the ion channel gene, but only patients with HCN4 mutation presented with a lower heart rate. Ion channel gene mutations should be searched systematically in patients with LVNC associated with either bradycardia or biventricular noncompaction, particularly when LV systolic function is preserved. Identifying causative mutations is of utmost importance for genetic counselling of at-risk relatives of patients affected by LVNC.
Sections du résumé
BACKGROUND
Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC).
METHODS AND RESULTS
From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18.5%; P < .001) than the 81 other patients with LVNC. Among them, both the 19 patients with an HCN4 mutation and the 11 patients with an RYR2 mutation presented with a higher LV ejection fraction and more frequent biventricular noncompaction than the 81 patients with LVNC but with no mutation in the ion channel gene, but only patients with HCN4 mutation presented with a lower heart rate.
CONCLUSIONS
Ion channel gene mutations should be searched systematically in patients with LVNC associated with either bradycardia or biventricular noncompaction, particularly when LV systolic function is preserved. Identifying causative mutations is of utmost importance for genetic counselling of at-risk relatives of patients affected by LVNC.
Identifiants
pubmed: 34088380
pii: S1071-9164(21)00010-5
doi: 10.1016/j.cardfail.2021.01.007
pii:
doi:
Substances chimiques
HCN4 protein, human
0
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
0
Ion Channels
0
Muscle Proteins
0
Potassium Channels
0
RyR2 protein, human
0
Ryanodine Receptor Calcium Release Channel
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
677-681Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.