例如:"lncRNA", "apoptosis", "WRKY"

Identification of Undetected Monogenic Cardiovascular Disorders.

J Am Coll Cardiol. 2020 Aug 18;76(7):797-808
Jawan W Abdulrahim 1 , Lydia Coulter Kwee 1 , Fawaz Alenezi 2 , Albert Y Sun 2 , Aris Baras 3 , Teminioluwa A Ajayi 4 , Ricardo Henao 5 , Christopher L Holley 2 , Robert W McGarrah 6 , James P Daubert 2 , Lauren K Truby 2 , Sreekanth Vemulapalli 2 , Andrew Wang 2 , Michel G Khouri 2 , Svati H Shah 7
Jawan W Abdulrahim 1 , Lydia Coulter Kwee 1 , Fawaz Alenezi 2 , Albert Y Sun 2 , Aris Baras 3 , Teminioluwa A Ajayi 4 , Ricardo Henao 5 , Christopher L Holley 2 , Robert W McGarrah 6 , James P Daubert 2 , Lauren K Truby 2 , Sreekanth Vemulapalli 2 , Andrew Wang 2 , Michel G Khouri 2 , Svati H Shah 7
+ et al

[No authors listed]

Author information
  • 1 Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina.
  • 2 Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • 3 Regeneron Genetics Center, Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • 4 Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
  • 5 Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina.
  • 6 Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • 7 Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. Electronic address: svati.shah@duke.edu.

摘要


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.

KEYWORDS: amyloidosis, exome sequencing, genetics, monogenic diseases