Genetic Association Between Hypoplastic Left Heart Syndrome and Cardiomyopathies.
Cardiac Myosins
/ genetics
Cardiomyopathy, Hypertrophic
/ genetics
Carrier Proteins
/ genetics
Case-Control Studies
Child
Codon, Nonsense
Female
Filamins
/ genetics
Genetic Predisposition to Disease
Heart Failure
/ therapy
Heart Transplantation
Heterozygote
Humans
Hypoplastic Left Heart Syndrome
/ genetics
Male
Mutation, Missense
Myosin Heavy Chains
/ genetics
Pedigree
Ryanodine Receptor Calcium Release Channel
/ genetics
Whole Genome Sequencing
cardiomyopathies
heart defects, congenital
heart failure
hypoplastic left heart syndrome
whole genome sequencing
Journal
Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
pubmed:
17
12
2020
medline:
4
1
2022
entrez:
16
12
2020
Statut:
ppublish
Résumé
Hypoplastic left heart syndrome (HLHS) with risk of poor outcome has been linked to Whole genome sequencing was performed in 197 probands with HLHS, 43 family members, and 813 controls. Data were filtered for rare, segregating variants in 3 index families comprised of an HLHS proband and relative(s) with cardiomyopathy. Whole genome sequencing data from cases and controls were compared for rare variant burden across 56 cardiomyopathy genes utilizing a weighted burden test approach, accounting for multiple testing using a Bonferroni correction. A pathogenic Whole genome sequencing in multiplex families, proband-parent trios, and case-control cohorts revealed defects in cardiomyopathy-associated genes in patients with HLHS, which may portend impaired functional reserve of the single-ventricle circulation.
Sections du résumé
BACKGROUND
Hypoplastic left heart syndrome (HLHS) with risk of poor outcome has been linked to
METHODS
Whole genome sequencing was performed in 197 probands with HLHS, 43 family members, and 813 controls. Data were filtered for rare, segregating variants in 3 index families comprised of an HLHS proband and relative(s) with cardiomyopathy. Whole genome sequencing data from cases and controls were compared for rare variant burden across 56 cardiomyopathy genes utilizing a weighted burden test approach, accounting for multiple testing using a Bonferroni correction.
RESULTS
A pathogenic
CONCLUSIONS
Whole genome sequencing in multiplex families, proband-parent trios, and case-control cohorts revealed defects in cardiomyopathy-associated genes in patients with HLHS, which may portend impaired functional reserve of the single-ventricle circulation.
Identifiants
pubmed: 33325730
doi: 10.1161/CIRCGEN.120.003126
doi:
Substances chimiques
Carrier Proteins
0
Codon, Nonsense
0
FLNC protein, human
0
Filamins
0
MYH6 protein, human
0
RyR2 protein, human
0
Ryanodine Receptor Calcium Release Channel
0
myosin-binding protein C
0
Cardiac Myosins
EC 3.6.1.-
Myosin Heavy Chains
EC 3.6.4.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM