PMID- 36768812
OWN - NLM
STAT- MEDLINE
DCOM- 20230216
LR  - 20230216
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 3
DP  - 2023 Jan 27
TI  - DSP-Related Cardiomyopathy as a Distinct Clinical Entity? Emerging Evidence from 
      an Italian Cohort.
LID - 10.3390/ijms24032490 [doi]
LID - 2490
AB  - Variants in desmoplakin gene (DSP MIM *125647) have been usually associated with 
      Arrhythmogenic Cardiomyopathy (ACM), or Dilated Cardiomyopathy (DCM) inherited in 
      an autosomal dominant manner. A cohort of 18 probands, characterized as 
      heterozygotes for DSP variants by a target Next Generation Sequencing (NGS) 
      cardiomyopathy panel, was analyzed. Cardiological, genetic data, and imaging 
      features were retrospectively collected. A total of 16 DSP heterozygous 
      pathogenic or likely pathogenic variants were identified, 75% (n = 12) truncating 
      variants, n = 2 missense variants, n = 1 splicing variant, and n = 1 duplication 
      variant. The mean age at diagnosis was 40.61 years (IQR 31-47.25), 61% of 
      patients being asymptomatic (n = 11, New York Heart Association (NYHA) class I) 
      and 39% mildly symptomatic (n = 7, NYHA class II). Notably, 39% of patients (n = 
      7) presented with a clinical history of presumed myocarditis episodes, 
      characterized by chest pain, myocardial enzyme release, 12-lead electrocardiogram 
      abnormalities with normal coronary arteries, which were recurrent in 57% of cases 
      (n = 4). About half of the patients (55%, n = 10) presented with a varied degree 
      of left ventricular enlargement (LVE), four showing biventricular involvement. 
      Eleven patients (61%) underwent implantable cardioverter defibrillator (ICD) 
      implantation, with a mean age of 46.81 years (IQR 36.00-64.00). Cardiac magnetic 
      resonance imaging (CMRI) identified in all 18 patients a delayed enhancement (DE) 
      area consistent with left ventricular (LV) myocardial fibrosis, with a larger 
      localization and extent in patients presenting with recurrent episodes of 
      myocardial injury. These clinical and genetic data confirm that DSP-related 
      cardiomyopathy may represent a distinct clinical entity characterized by a high 
      arrhythmic burden, variable degrees of LVE, Late Gadolinium Enhancement (LGE) 
      with subepicardial distribution and episodes of myocarditis-like picture.
FAU - Di Lorenzo, Francesca
AU  - Di Lorenzo F
AUID- ORCID: 0000-0001-8574-337X
AD  - Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via 
      Montpellier 1, 00133 Rome, Italy.
FAU - Marchionni, Enrica
AU  - Marchionni E
AUID- ORCID: 0000-0002-0341-6461
AD  - Medical Genetics, Policlinico Tor Vergata, 00133 Rome, Italy.
FAU - Ferradini, Valentina
AU  - Ferradini V
AD  - Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via 
      Montpellier 1, 00133 Rome, Italy.
FAU - Latini, Andrea
AU  - Latini A
AD  - Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via 
      Montpellier 1, 00133 Rome, Italy.
FAU - Pezzoli, Laura
AU  - Pezzoli L
AUID- ORCID: 0000-0002-8111-563X
AD  - Laboratory of Medical Genetics, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy.
FAU - Martino, Annamaria
AU  - Martino A
AD  - Department of Cardiology, Policlinico Casilino, 00169 Rome, Italy.
FAU - Romeo, Fabiana
AU  - Romeo F
AUID- ORCID: 0000-0001-8604-4925
AD  - Department of Cardiology, Policlinico Casilino, 00169 Rome, Italy.
FAU - Iorio, Annamaria
AU  - Iorio A
AD  - Cardiology Department, ASST Papa Giovanni XXIII Bergamo, 24127 Bergamo, Italy.
FAU - Bianchi, Stefano
AU  - Bianchi S
AD  - UOC Cardiologia, Ospedale Fatebenefratelli Isola Tiberina, 00186 Rome, Italy.
FAU - Iascone, Maria
AU  - Iascone M
AUID- ORCID: 0000-0002-4707-212X
AD  - Laboratory of Medical Genetics, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy.
FAU - Calo, Leonardo
AU  - Calo L
AD  - Department of Cardiology, Policlinico Casilino, 00169 Rome, Italy.
FAU - Novelli, Giuseppe
AU  - Novelli G
AUID- ORCID: 0000-0002-7781-602X
AD  - Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via 
      Montpellier 1, 00133 Rome, Italy.
FAU - Mango, Ruggiero
AU  - Mango R
AD  - House of Care D4, Local Health Authority Roma 2, 00185 Rome, Italy.
FAU - Sangiuolo, Federica
AU  - Sangiuolo F
AUID- ORCID: 0000-0002-6227-4248
AD  - Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via 
      Montpellier 1, 00133 Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20230127
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Contrast Media)
RN  - AU0V1LM3JT (Gadolinium)
RN  - 0 (DSP protein, human)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Middle Aged
MH  - *Cardiomyopathies/etiology/genetics
MH  - Contrast Media
MH  - Gadolinium
MH  - Hypertrophy, Left Ventricular
MH  - *Myocarditis
MH  - Retrospective Studies
PMC - PMC9916412
OTO - NOTNLM
OT  - arrhythmogenic cardiomyopathy
OT  - desmoplakin
OT  - dilated cardiomyopathy
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/12 06:00
MHDA- 2023/02/15 06:00
PMCR- 2023/01/27
CRDT- 2023/02/11 01:22
PHST- 2023/01/13 00:00 [received]
PHST- 2023/01/23 00:00 [revised]
PHST- 2023/01/23 00:00 [accepted]
PHST- 2023/02/11 01:22 [entrez]
PHST- 2023/02/12 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
PHST- 2023/01/27 00:00 [pmc-release]
AID - ijms24032490 [pii]
AID - ijms-24-02490 [pii]
AID - 10.3390/ijms24032490 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jan 27;24(3):2490. doi: 10.3390/ijms24032490.