PMID- 34067482
OWN - NLM
STAT- MEDLINE
DCOM- 20211227
LR  - 20211227
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 12
IP  - 6
DP  - 2021 May 22
TI  - Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy.
LID - 10.3390/genes12060793 [doi]
LID - 793
AB  - BACKGROUND: Arrhythmogenic Cardiomyopathy (ACM) is a disease of the cardiac 
      muscle, characterized by frequent ventricular arrhythmias and functional/ 
      structural abnormalities, mainly of the right ventricle. To date, 20 different 
      genes have been associated with ACM and the majority of them encode for 
      desmosomal proteins. In this study, we describe the characterization of two novel 
      variants in MHY7 gene, segregating in two ACM families. MYH7 encodes for myosin 
      heavy chain beta (MHC-beta) isoform, involved in cardiac muscle contractility. METHOD 
      AND RESULTS: In family A, the autopsy revealed ACM with biventricular involvement 
      in both the proband and his father. In family B, the proband had been diagnosed 
      as affected by ACM and implanted with implantable cardioverter defibrillator 
      (ICD), due to ECG evidence of monomorphic ventricular tachycardia after syncope. 
      After clinical evaluation, a molecular diagnosis was performed using a NGS custom 
      panel. The two novel variants identified predicted damaging, located in a highly 
      conserved domain: c. 2630T>C is not described while c.2609G>A has a frequency of 
      0.00000398. In silico analyses evaluated the docking characteristics between 
      proteins using the Haddock2.2 webserver. CONCLUSIONS: Our results reveal two 
      variants in sarcomeric genes to be the molecular cause of ACM, further increasing 
      the genetic heterogeneity of the disease; in fact, sarcomeric variants are 
      usually associated with HCM phenotype. Studies on the role of sarcomere genes in 
      the pathogenesis of ACM are surely recommended in those ACM patients negative for 
      desmosomal mutation screening.
FAU - Ferradini, Valentina
AU  - Ferradini V
AD  - Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 
      Rome, Italy.
FAU - Parca, Luca
AU  - Parca L
AD  - Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
FAU - Martino, Annamaria
AU  - Martino A
AD  - Division of Cardiology, Policlinico Casilino, 00169 Rome, Italy.
FAU - Lanzillo, Chiara
AU  - Lanzillo C
AD  - Division of Cardiology, Policlinico Casilino, 00169 Rome, Italy.
FAU - Silvetti, Elisa
AU  - Silvetti E
AD  - Division of Cardiology, Policlinico Casilino, 00169 Rome, Italy.
FAU - Calo, Leonardo
AU  - Calo L
AUID- ORCID: 0000-0002-6062-5286
AD  - Division of Cardiology, Policlinico Casilino, 00169 Rome, Italy.
FAU - Caselli, Stefano
AU  - Caselli S
AD  - Cardiovascular Center Zurich, 8091 Zurich, Switzerland.
FAU - Novelli, Giuseppe
AU  - Novelli G
AD  - Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 
      Rome, Italy.
AD  - IRCCS Neuromed, 86077 Pozzilli, Italy.
AD  - Department of Pharmacology, School of Medicine, University of Nevada, Reno, NV 
      89557, USA.
FAU - Helmer-Citterich, Manuela
AU  - Helmer-Citterich M
AUID- ORCID: 0000-0001-9530-7504
AD  - Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
FAU - Sangiuolo, Federica Carla
AU  - Sangiuolo FC
AUID- ORCID: 0000-0002-6227-4248
AD  - Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 
      Rome, Italy.
FAU - Mango, Ruggiero
AU  - Mango R
AD  - Cardiology Unit, Department of Emergency and Critical Care, Tor Vergata Hospital, 
      00133 Rome, Italy.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20210522
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (MYH7 protein, human)
RN  - EC 3.6.1.- (Cardiac Myosins)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Arrhythmias, Cardiac/complications/*genetics/pathology
MH  - Cardiac Myosins/*genetics
MH  - Cardiomyopathy, Hypertrophic/etiology/*genetics/pathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Myosin Heavy Chains/*genetics
MH  - Pedigree
PMC - PMC8224781
OTO - NOTNLM
OT  - MYH7 gene
OT  - arrhythmogenic cardiomyopathy
OT  - hypertrophic cardiomyopathy
OT  - sudden cardiac death
OT  - targeted gene panel
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/12/28 06:00
PMCR- 2021/05/22
CRDT- 2021/06/02 01:19
PHST- 2021/05/04 00:00 [received]
PHST- 2021/05/14 00:00 [revised]
PHST- 2021/05/20 00:00 [accepted]
PHST- 2021/06/02 01:19 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/12/28 06:00 [medline]
PHST- 2021/05/22 00:00 [pmc-release]
AID - genes12060793 [pii]
AID - genes-12-00793 [pii]
AID - 10.3390/genes12060793 [doi]
PST - epublish
SO  - Genes (Basel). 2021 May 22;12(6):793. doi: 10.3390/genes12060793.