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Arrhythmogenic right ventricular dysplasia 9(ARVD9)

MedGen UID:
373205
•Concept ID:
C1836906
•
Disease or Syndrome
Synonyms: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 9; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 9; ARVD9
 
Gene (location): PKP2 (12p11.21)
 
Monarch Initiative: MONDO:0012180
OMIM®: 609040

Definition

ARVC may not cause any symptoms in its early stages. However, affected individuals may still be at risk of sudden death, especially during strenuous exercise. When symptoms occur, they most commonly include a sensation of fluttering or pounding in the chest (palpitations), light-headedness, and fainting (syncope). Over time, ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen. If the myocardium becomes severely damaged in the later stages of the disease, it can lead to heart failure.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of heart disease that usually appears in adulthood. ARVC is a disorder of the myocardium, which is the muscular wall of the heart. This condition causes part of the myocardium to break down over time, increasing the risk of an abnormal heartbeat (arrhythmia) and sudden death. [from MedlinePlus Genetics]

Clinical features

From HPO
Sudden cardiac death
MedGen UID:
38841
•Concept ID:
C0085298
•
Pathologic Function
The heart suddenly and unexpectedly stops beating resulting in death within a short time period (generally within 1 h of symptom onset).
See: Feature record | Search on this feature
Cardiac arrest
MedGen UID:
5456
•Concept ID:
C0018790
•
Finding
An abrupt loss of heart function.
See: Feature record | Search on this feature
Palpitations
MedGen UID:
14579
•Concept ID:
C0030252
•
Finding
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
See: Feature record | Search on this feature
Syncope
MedGen UID:
21443
•Concept ID:
C0039070
•
Sign or Symptom
Syncope is a syndrome in which loss of consciousness is of relatively sudden onset, temporary (usually less than 1 to 2 minutes), self-terminating, and of usually rapid recovery. Syncope leads to a generalized weakness of muscles with loss of postural tone, inability to stand upright, and loss of consciousness. Once the patient is in a horizontal position, blood flow to the brain is no longer hindered by gravitation and consciousness is regained. Unconsciousness usually lasts for seconds to minutes. Headache and drowsiness (which usually follow seizures) do not follow a syncopal attack. Syncope results from a sudden impairment of brain metabolism usually due to a reduction in cerebral blood flow.
See: Feature record | Search on this feature
Ventricular tachycardia
MedGen UID:
12068
•Concept ID:
C0042514
•
Finding
A tachycardia originating in the ventricles characterized by rapid heart rate (over 100 beats per minute) and broad QRS complexes (over 120 ms).
See: Feature record | Search on this feature
Premature ventricular contraction
MedGen UID:
56236
•Concept ID:
C0151636
•
Disease or Syndrome
Premature ventricular contractions (PVC) or ventricular extrasystoles are premature contractions of the heart that arise in response to an impulse in the ventricles rather than the normal impulse from the sinoatrial (SA) node.
See: Feature record | Search on this feature
Prolonged QRS complex
MedGen UID:
489828
•Concept ID:
C0235475
•
Finding
Increased time for the complex comprised of the Q wave, R wave, and S wave as measured by the electrocardiogram (EKG).. In adults, normal values are 0.06 - 0.10 sec.
See: Feature record | Search on this feature
Fibrofatty replacement of right ventricular myocardium
MedGen UID:
369873
•Concept ID:
C1968863
•
Pathologic Function
Replacement of the myocardium of the right ventricular free wall by fat and fibrous tissue.
See: Feature record | Search on this feature
Right ventricular cardiomyopathy
MedGen UID:
384481
•Concept ID:
C2063326
•
Disease or Syndrome
Right ventricular dysfunction (global or regional) with functional and morphological right ventricular abnormalities, with or without left ventricular disease.
See: Feature record | Search on this feature
Dilatation of the ventricular cavity
MedGen UID:
1393082
•Concept ID:
C4476545
•
Anatomical Abnormality
A localized outpouching of ventricular cavity that is generally associated with dyskinesia and paradoxical expansion during systole.
See: Feature record | Search on this feature
Epsilon wave
MedGen UID:
1815063
•Concept ID:
C5706157
•
Finding
An electric signal of depolarization observed between the end of the QRS complex and the beginning of the T wave.
See: Feature record | Search on this feature
Dyspnea
MedGen UID:
3938
•Concept ID:
C0013404
•
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Modified mRNA Treatment Restores Cardiac Function in Desmocollin-2-Deficient Mouse Models of Arrhythmogenic Right Ventricular Cardiomyopathy.
Zou Y, Lu J, Lian Z, Jia J, Shen J, Li Q, Wong JMJ, Jin K, Yan W, Ren X, Zhang Y, Huang C, Yang H, Huang F, Li J, Zhai J, Xu Y, Xu X, Yu H, Jin Y, Gong H, Lin J, Ge J, Dai Y
Circulation 2025 Jun 24;151(25):1780-1796. Epub 2025 Apr 11 doi: 10.1161/CIRCULATIONAHA.124.072340. PMID: 40211944Free PMC Article
Molecular genetics in 4408 cardiomyopathy probands and 3008 relatives in Norway: 17 years of genetic testing in a national laboratory.
Stava TT, Leren TP, Bogsrud MP
Eur J Prev Cardiol 2022 Oct 18;29(13):1789-1799. doi: 10.1093/eurjpc/zwac102. PMID: 35653365
Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria.
Corrado D, Perazzolo Marra M, Zorzi A, Beffagna G, Cipriani A, Lazzari M, Migliore F, Pilichou K, Rampazzo A, Rigato I, Rizzo S, Thiene G, Anastasakis A, Asimaki A, Bucciarelli-Ducci C, Haugaa KH, Marchlinski FE, Mazzanti A, McKenna WJ, Pantazis A, Pelliccia A, Schmied C, Sharma S, Wichter T, Bauce B, Basso C
Int J Cardiol 2020 Nov 15;319:106-114. Epub 2020 Jun 16 doi: 10.1016/j.ijcard.2020.06.005. PMID: 32561223

Recent clinical studies

Etiology

Natural History and Clinical Outcomes of Patients With DSG2/DSC2 Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy.
Chen L, Hu Y, Saguner AM, Bauce B, Liu Y, Shi A, Guan F, Chen Z, Bueno Marinas M, Wu L, Foltran D, Hermida A, Fressart V, Pinci S, Celeghin R, Chen Z, Zhang B, Lin Y, Liu X, Cason M, Martini M, Rigato I, Brunckhorst C, Biller R, Basso C, Yang B, Zhao X, Cadrin-Tourigny J, Gasperetti A, James CA, Zhou X, Gandjbakhch E, Pilichou K, Duru F, Hu S
Circulation 2025 Apr 29;151(17):1213-1230. Epub 2025 Mar 24 doi: 10.1161/CIRCULATIONAHA.124.072226. PMID: 40123482
Clinical features and outcomes in carriers of pathogenic desmoplakin variants.
Gasperetti A, Carrick RT, Protonotarios A, Murray B, Laredo M, van der Schaaf I, Lekanne RH, Syrris P, Cannie D, Tichnell C, Cappelletto C, Gigli M, Medo K, Saguner AM, Duru F, Gilotra NA, Zimmerman S, Hylind R, Abrams DJ, Lakdawala NK, Cadrin-Tourigny J, Targetti M, Olivotto I, Graziosi M, Cox M, Biagini E, Charron P, Casella M, Tondo C, Yazdani M, Ware JS, Prasad SK, Calò L, Smith ED, Helms AS, Hespe S, Ingles J, Tandri H, Ader F, Peretto G, Peters S, Horton A, Yao J, Dittmann S, Schulze-Bahr E, Qureshi M, Young K, Carruth ED, Haggerty C, Parikh VN, Taylor M, Mestroni L, Wilde A, Sinagra G, Merlo M, Gandjbakhch E, van Tintelen JP, Te Riele ASJM, Elliott PM, Calkins H, James CA
Eur Heart J 2025 Jan 21;46(4):362-376. doi: 10.1093/eurheartj/ehae571. PMID: 39288222Free PMC Article
Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.
Bermudez-Jimenez FJ, Protonotarios A, García-Hernández S, Pérez Asensio A, Rampazzo A, Zorio E, Brodehl A, Arias MA, Macías-Ruiz R, Fernández-Armenta J, Remior Perez P, Muñoz-Esparza C, Pilichou K, Bauce B, Merino JL, Moliner-Abós C, Ochoa JP, Barriales-Villa R, Garcia-Pavia P, Lopes LR, Syrris P, Corrado D, Elliott PM, McKenna WJ, Jimenez-Jaimez J
JACC Clin Electrophysiol 2024 Jun;10(6):1178-1190. Epub 2024 May 8 doi: 10.1016/j.jacep.2024.02.031. PMID: 38727660
Molecular genetics in 4408 cardiomyopathy probands and 3008 relatives in Norway: 17 years of genetic testing in a national laboratory.
Stava TT, Leren TP, Bogsrud MP
Eur J Prev Cardiol 2022 Oct 18;29(13):1789-1799. doi: 10.1093/eurjpc/zwac102. PMID: 35653365
Dilated cardiomyopathy: the complexity of a diverse genetic architecture.
Hershberger RE, Hedges DJ, Morales A
Nat Rev Cardiol 2013 Sep;10(9):531-47. Epub 2013 Jul 30 doi: 10.1038/nrcardio.2013.105. PMID: 23900355

Diagnosis

Natural History and Clinical Outcomes of Patients With DSG2/DSC2 Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy.
Chen L, Hu Y, Saguner AM, Bauce B, Liu Y, Shi A, Guan F, Chen Z, Bueno Marinas M, Wu L, Foltran D, Hermida A, Fressart V, Pinci S, Celeghin R, Chen Z, Zhang B, Lin Y, Liu X, Cason M, Martini M, Rigato I, Brunckhorst C, Biller R, Basso C, Yang B, Zhao X, Cadrin-Tourigny J, Gasperetti A, James CA, Zhou X, Gandjbakhch E, Pilichou K, Duru F, Hu S
Circulation 2025 Apr 29;151(17):1213-1230. Epub 2025 Mar 24 doi: 10.1161/CIRCULATIONAHA.124.072226. PMID: 40123482
Clinical features and outcomes in carriers of pathogenic desmoplakin variants.
Gasperetti A, Carrick RT, Protonotarios A, Murray B, Laredo M, van der Schaaf I, Lekanne RH, Syrris P, Cannie D, Tichnell C, Cappelletto C, Gigli M, Medo K, Saguner AM, Duru F, Gilotra NA, Zimmerman S, Hylind R, Abrams DJ, Lakdawala NK, Cadrin-Tourigny J, Targetti M, Olivotto I, Graziosi M, Cox M, Biagini E, Charron P, Casella M, Tondo C, Yazdani M, Ware JS, Prasad SK, Calò L, Smith ED, Helms AS, Hespe S, Ingles J, Tandri H, Ader F, Peretto G, Peters S, Horton A, Yao J, Dittmann S, Schulze-Bahr E, Qureshi M, Young K, Carruth ED, Haggerty C, Parikh VN, Taylor M, Mestroni L, Wilde A, Sinagra G, Merlo M, Gandjbakhch E, van Tintelen JP, Te Riele ASJM, Elliott PM, Calkins H, James CA
Eur Heart J 2025 Jan 21;46(4):362-376. doi: 10.1093/eurheartj/ehae571. PMID: 39288222Free PMC Article
Molecular genetics in 4408 cardiomyopathy probands and 3008 relatives in Norway: 17 years of genetic testing in a national laboratory.
Stava TT, Leren TP, Bogsrud MP
Eur J Prev Cardiol 2022 Oct 18;29(13):1789-1799. doi: 10.1093/eurjpc/zwac102. PMID: 35653365
Arrhythmogenic left ventricular cardiomyopathy.
Corrado D, Basso C
Heart 2022 May;108(9):733-743. Epub 2021 Jul 13 doi: 10.1136/heartjnl-2020-316944. PMID: 34257076Free PMC Article
Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria.
Corrado D, Perazzolo Marra M, Zorzi A, Beffagna G, Cipriani A, Lazzari M, Migliore F, Pilichou K, Rampazzo A, Rigato I, Rizzo S, Thiene G, Anastasakis A, Asimaki A, Bucciarelli-Ducci C, Haugaa KH, Marchlinski FE, Mazzanti A, McKenna WJ, Pantazis A, Pelliccia A, Schmied C, Sharma S, Wichter T, Bauce B, Basso C
Int J Cardiol 2020 Nov 15;319:106-114. Epub 2020 Jun 16 doi: 10.1016/j.ijcard.2020.06.005. PMID: 32561223

Therapy

Modified mRNA Treatment Restores Cardiac Function in Desmocollin-2-Deficient Mouse Models of Arrhythmogenic Right Ventricular Cardiomyopathy.
Zou Y, Lu J, Lian Z, Jia J, Shen J, Li Q, Wong JMJ, Jin K, Yan W, Ren X, Zhang Y, Huang C, Yang H, Huang F, Li J, Zhai J, Xu Y, Xu X, Yu H, Jin Y, Gong H, Lin J, Ge J, Dai Y
Circulation 2025 Jun 24;151(25):1780-1796. Epub 2025 Apr 11 doi: 10.1161/CIRCULATIONAHA.124.072340. PMID: 40211944Free PMC Article
Arrhythmogenic Right Ventricular Cardiomyopathy: Diagnosis, Risk Stratification, and Treatment.
Kreimer F, Saguner AM, Akin I, LastName FM, LastName FM, LastName FM
Dtsch Arztebl Int 2025 May 2;122(9):229-234. doi: 10.3238/arztebl.m2024.0264. PMID: 40202346
Diagnostic and therapeutic strategies for arrhythmogenic right ventricular dysplasia/cardiomyopathy patient.
Wang W, James CA, Calkins H
Europace 2019 Jan 1;21(1):9-21. doi: 10.1093/europace/euy063. PMID: 29688316Free PMC Article
Pregnancy and newborn outcomes in arrhythmogenic right ventricular cardiomyopathy/dysplasia.
Gandjbakhch E, Varlet E, Duthoit G, Fressart V, Charron P, Himbert C, Maupain C, Bordet C, Hidden-Lucet F, Nizard J
Int J Cardiol 2018 May 1;258:172-178. doi: 10.1016/j.ijcard.2017.11.067. PMID: 29544927
Radiofrequency Ablation in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC).
Romero J, Grushko M, Briceño DF, Natale A, Di Biase L
Curr Cardiol Rep 2017 Sep;19(9):82. doi: 10.1007/s11886-017-0893-3. PMID: 28779285

Prognosis

Clinical features and outcomes in carriers of pathogenic desmoplakin variants.
Gasperetti A, Carrick RT, Protonotarios A, Murray B, Laredo M, van der Schaaf I, Lekanne RH, Syrris P, Cannie D, Tichnell C, Cappelletto C, Gigli M, Medo K, Saguner AM, Duru F, Gilotra NA, Zimmerman S, Hylind R, Abrams DJ, Lakdawala NK, Cadrin-Tourigny J, Targetti M, Olivotto I, Graziosi M, Cox M, Biagini E, Charron P, Casella M, Tondo C, Yazdani M, Ware JS, Prasad SK, Calò L, Smith ED, Helms AS, Hespe S, Ingles J, Tandri H, Ader F, Peretto G, Peters S, Horton A, Yao J, Dittmann S, Schulze-Bahr E, Qureshi M, Young K, Carruth ED, Haggerty C, Parikh VN, Taylor M, Mestroni L, Wilde A, Sinagra G, Merlo M, Gandjbakhch E, van Tintelen JP, Te Riele ASJM, Elliott PM, Calkins H, James CA
Eur Heart J 2025 Jan 21;46(4):362-376. doi: 10.1093/eurheartj/ehae571. PMID: 39288222Free PMC Article
Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.
Bermudez-Jimenez FJ, Protonotarios A, García-Hernández S, Pérez Asensio A, Rampazzo A, Zorio E, Brodehl A, Arias MA, Macías-Ruiz R, Fernández-Armenta J, Remior Perez P, Muñoz-Esparza C, Pilichou K, Bauce B, Merino JL, Moliner-Abós C, Ochoa JP, Barriales-Villa R, Garcia-Pavia P, Lopes LR, Syrris P, Corrado D, Elliott PM, McKenna WJ, Jimenez-Jaimez J
JACC Clin Electrophysiol 2024 Jun;10(6):1178-1190. Epub 2024 May 8 doi: 10.1016/j.jacep.2024.02.031. PMID: 38727660
A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.
Cadrin-Tourigny J, Bosman LP, Nozza A, Wang W, Tadros R, Bhonsale A, Bourfiss M, Fortier A, Lie ØH, Saguner AM, Svensson A, Andorin A, Tichnell C, Murray B, Zeppenfeld K, van den Berg MP, Asselbergs FW, Wilde AAM, Krahn AD, Talajic M, Rivard L, Chelko S, Zimmerman SL, Kamel IR, Crosson JE, Judge DP, Yap SC, van der Heijden JF, Tandri H, Jongbloed JDH, Guertin MC, van Tintelen JP, Platonov PG, Duru F, Haugaa KH, Khairy P, Hauer RNW, Calkins H, Te Riele ASJM, James CA
Eur Heart J 2022 Aug 21;43(32):e1-e9. doi: 10.1093/eurheartj/ehac180. PMID: 35441664Free PMC Article
Diagnostic and therapeutic strategies for arrhythmogenic right ventricular dysplasia/cardiomyopathy patient.
Wang W, James CA, Calkins H
Europace 2019 Jan 1;21(1):9-21. doi: 10.1093/europace/euy063. PMID: 29688316Free PMC Article
Myocardial voltage ratio in arrhythmogenic right ventricular dysplasia/cardiomyopathy.
Müssigbrodt A, Bertagnolli L, Efimova E, Kosiuk J, Dinov B, Bode K, Kircher S, Dagres N, Döring M, Richter S, Sommer P, Husser D, Bollmann A, Hindricks G, Arya A
Herzschrittmacherther Elektrophysiol 2017 Jun;28(2):219-224. Epub 2017 May 23 doi: 10.1007/s00399-017-0508-0. PMID: 28536891

Clinical prediction guides

Clinical features and outcomes in carriers of pathogenic desmoplakin variants.
Gasperetti A, Carrick RT, Protonotarios A, Murray B, Laredo M, van der Schaaf I, Lekanne RH, Syrris P, Cannie D, Tichnell C, Cappelletto C, Gigli M, Medo K, Saguner AM, Duru F, Gilotra NA, Zimmerman S, Hylind R, Abrams DJ, Lakdawala NK, Cadrin-Tourigny J, Targetti M, Olivotto I, Graziosi M, Cox M, Biagini E, Charron P, Casella M, Tondo C, Yazdani M, Ware JS, Prasad SK, Calò L, Smith ED, Helms AS, Hespe S, Ingles J, Tandri H, Ader F, Peretto G, Peters S, Horton A, Yao J, Dittmann S, Schulze-Bahr E, Qureshi M, Young K, Carruth ED, Haggerty C, Parikh VN, Taylor M, Mestroni L, Wilde A, Sinagra G, Merlo M, Gandjbakhch E, van Tintelen JP, Te Riele ASJM, Elliott PM, Calkins H, James CA
Eur Heart J 2025 Jan 21;46(4):362-376. doi: 10.1093/eurheartj/ehae571. PMID: 39288222Free PMC Article
Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.
Bermudez-Jimenez FJ, Protonotarios A, García-Hernández S, Pérez Asensio A, Rampazzo A, Zorio E, Brodehl A, Arias MA, Macías-Ruiz R, Fernández-Armenta J, Remior Perez P, Muñoz-Esparza C, Pilichou K, Bauce B, Merino JL, Moliner-Abós C, Ochoa JP, Barriales-Villa R, Garcia-Pavia P, Lopes LR, Syrris P, Corrado D, Elliott PM, McKenna WJ, Jimenez-Jaimez J
JACC Clin Electrophysiol 2024 Jun;10(6):1178-1190. Epub 2024 May 8 doi: 10.1016/j.jacep.2024.02.031. PMID: 38727660
A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.
Cadrin-Tourigny J, Bosman LP, Nozza A, Wang W, Tadros R, Bhonsale A, Bourfiss M, Fortier A, Lie ØH, Saguner AM, Svensson A, Andorin A, Tichnell C, Murray B, Zeppenfeld K, van den Berg MP, Asselbergs FW, Wilde AAM, Krahn AD, Talajic M, Rivard L, Chelko S, Zimmerman SL, Kamel IR, Crosson JE, Judge DP, Yap SC, van der Heijden JF, Tandri H, Jongbloed JDH, Guertin MC, van Tintelen JP, Platonov PG, Duru F, Haugaa KH, Khairy P, Hauer RNW, Calkins H, Te Riele ASJM, James CA
Eur Heart J 2022 Aug 21;43(32):e1-e9. doi: 10.1093/eurheartj/ehac180. PMID: 35441664Free PMC Article
Diagnostic and therapeutic strategies for arrhythmogenic right ventricular dysplasia/cardiomyopathy patient.
Wang W, James CA, Calkins H
Europace 2019 Jan 1;21(1):9-21. doi: 10.1093/europace/euy063. PMID: 29688316Free PMC Article
Dilated cardiomyopathy: the complexity of a diverse genetic architecture.
Hershberger RE, Hedges DJ, Morales A
Nat Rev Cardiol 2013 Sep;10(9):531-47. Epub 2013 Jul 30 doi: 10.1038/nrcardio.2013.105. PMID: 23900355

Recent systematic reviews

Myocarditis-like Episodes in Patients with Arrhythmogenic Cardiomyopathy: A Systematic Review on the So-Called Hot-Phase of the Disease.
Bariani R, Rigato I, Cipriani A, Bueno Marinas M, Celeghin R, Basso C, Corrado D, Pilichou K, Bauce B
Biomolecules 2022 Sep 19;12(9) doi: 10.3390/biom12091324. PMID: 36139162Free PMC Article
Prevalence of atrial arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy: a systematic review and meta-analysis.
Rujirachun P, Wattanachayakul P, Charoenngam N, Winijkul A, Ungprasert P
J Cardiovasc Med (Hagerstown) 2020 May;21(5):368-376. doi: 10.2459/JCM.0000000000000962. PMID: 32243340
The efficacy and safety of electroanatomic mapping-guided endomyocardial biopsy: a systematic review.
Vaidya VR, Abudan AA, Vasudevan K, Shantha G, Cooper LT, Kapa S, Noseworthy PA, Cha YM, Asirvatham SJ, Deshmukh AJ
J Interv Card Electrophysiol 2018 Oct;53(1):63-71. Epub 2018 Jul 12 doi: 10.1007/s10840-018-0410-7. PMID: 30003460
Systematic review: Impact of the new task force criteria in the diagnosis of arrhythmogenic right ventricular cardiomyopathy.
Femia G, Sy RW, Puranik R
Int J Cardiol 2017 Aug 15;241:311-317. Epub 2017 Mar 19 doi: 10.1016/j.ijcard.2017.03.069. PMID: 28342631
Genotype-phenotype relationship in patients with arrhythmogenic right ventricular cardiomyopathy caused by desmosomal gene mutations: A systematic review and meta-analysis.
Xu Z, Zhu W, Wang C, Huang L, Zhou Q, Hu J, Cheng X, Hong K
Sci Rep 2017 Jan 25;7:41387. doi: 10.1038/srep41387. PMID: 28120905Free PMC Article

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