Identification of Undetected Monogenic Cardiovascular Disorders.
Cardiovascular Diseases
/ classification
Electronic Health Records
Female
Genetic Testing
/ methods
Genomic Structural Variation
Hemochromatosis Protein
/ genetics
Humans
Male
Middle Aged
Missed Diagnosis
/ prevention & control
Prevalence
Sequence Deletion
United States
/ epidemiology
Exome Sequencing
/ methods
alpha-Glucosidases
/ genetics
amyloidosis
exome sequencing
genetics
monogenic diseases
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
18 08 2020
18 08 2020
Historique:
received:
27
03
2020
revised:
14
06
2020
accepted:
15
06
2020
entrez:
15
8
2020
pubmed:
15
8
2020
medline:
23
1
2021
Statut:
ppublish
Résumé
Monogenic diseases are individually rare but collectively common, and are likely underdiagnosed. The purpose of this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentially missed diagnoses in a cardiovascular cohort. Exomes from 8,574 individuals referred for cardiac catheterization were analyzed. Pathogenic/likely pathogenic (P/LP) variants associated with MCVD (cardiomyopathies, arrhythmias, connective tissue disorders, and familial hypercholesterolemia were identified. Electronic health records (EHRs) were reviewed for individuals harboring P/LP variants who were predicted to develop disease (G+). G+ individuals who did not have a documented relevant diagnosis were classified into groups of whether they may represent missed diagnoses (unknown, unlikely, possible, probable, or definite) based on relevant diagnostic criteria/features for that disease. In total, 159 P/LP variants were identified; 2,361 individuals harbored at least 1 P/LP variant, of whom 389 G+ individuals (4.5% of total cohort) were predicted to have at least 1 MCVD. EHR review of 342 G+ individuals predicted to have 1 MCVD with sufficient EHR data revealed that 52 had been given the relevant clinical diagnosis. The remaining 290 individuals were classified as potentially having an MCVD as follows: 193 unlikely (66.6%), 50 possible (17.2%), 30 probable (10.3%), and 17 definite (5.9%). Grouping possible, probable, definite, and known diagnoses, 149 were considered to have an MCVD. Novel MCVD pathogenic variants were identified in 16 individuals. Overall, 149 individuals (1.7% of cohort) had MCVDs, but only 35% were diagnosed. These patients represents a "missed opportunity," which could be addressed by greater use of genetic testing of patients seen by cardiologists.
Sections du résumé
BACKGROUND
Monogenic diseases are individually rare but collectively common, and are likely underdiagnosed.
OBJECTIVES
The purpose of this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentially missed diagnoses in a cardiovascular cohort.
METHODS
Exomes from 8,574 individuals referred for cardiac catheterization were analyzed. Pathogenic/likely pathogenic (P/LP) variants associated with MCVD (cardiomyopathies, arrhythmias, connective tissue disorders, and familial hypercholesterolemia were identified. Electronic health records (EHRs) were reviewed for individuals harboring P/LP variants who were predicted to develop disease (G+). G+ individuals who did not have a documented relevant diagnosis were classified into groups of whether they may represent missed diagnoses (unknown, unlikely, possible, probable, or definite) based on relevant diagnostic criteria/features for that disease.
RESULTS
In total, 159 P/LP variants were identified; 2,361 individuals harbored at least 1 P/LP variant, of whom 389 G+ individuals (4.5% of total cohort) were predicted to have at least 1 MCVD. EHR review of 342 G+ individuals predicted to have 1 MCVD with sufficient EHR data revealed that 52 had been given the relevant clinical diagnosis. The remaining 290 individuals were classified as potentially having an MCVD as follows: 193 unlikely (66.6%), 50 possible (17.2%), 30 probable (10.3%), and 17 definite (5.9%). Grouping possible, probable, definite, and known diagnoses, 149 were considered to have an MCVD. Novel MCVD pathogenic variants were identified in 16 individuals.
CONCLUSIONS
Overall, 149 individuals (1.7% of cohort) had MCVDs, but only 35% were diagnosed. These patients represents a "missed opportunity," which could be addressed by greater use of genetic testing of patients seen by cardiologists.
Identifiants
pubmed: 32792077
pii: S0735-1097(20)35733-8
doi: 10.1016/j.jacc.2020.06.037
pmc: PMC7428466
mid: NIHMS1613641
pii:
doi:
Substances chimiques
HFE protein, human
0
Hemochromatosis Protein
0
GAA protein, human
EC 3.2.1.20
alpha-Glucosidases
EC 3.2.1.20
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
797-808Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL036587
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002553
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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