PMID- 32005173
OWN - NLM
STAT- MEDLINE
DCOM- 20200303
LR  - 20231113
IS  - 1471-2350 (Electronic)
IS  - 1471-2350 (Linking)
VI  - 21
IP  - 1
DP  - 2020 Jan 31
TI  - DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe 
      arrhythmias and left ventricular cardiomyopathy.
PG  - 19
LID - 10.1186/s12881-020-0955-z [doi]
LID - 19
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is a condition characterized by 
      dilatation and systolic dysfunction of the left ventricle in the absence of 
      severe coronary artery disease or abnormal loading conditions. Mutations in the 
      titin (TTN) and lamin A/C (LMNA) genes are the two most significant contributors 
      in familial DCM. Previously mutations in the desmoplakin (DSP) gene have been 
      associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) and more 
      recently with DCM. METHODS: We describe the cardiac phenotype related to a DSP 
      mutation which was identified in ten unrelated Finnish index patients using 
      next-generation sequencing. Sanger sequencing was used to verify the presence of 
      this DSP variant in the probands' relatives. Medical records were obtained, and 
      clinical evaluation was performed. RESULTS: We identified DSP c.6310delA, 
      p.(Thr2104Glnfs*12) variant in 17 individuals of which 11 (65%) fulfilled the DCM 
      diagnostic criteria. This pathogenic variant presented with left ventricular 
      dilatation, dysfunction and major ventricular arrhythmias. Two patients showed 
      late gadolinium enhancement (LGE) and myocardial edema on cardiac magnetic 
      resonance imaging (MRI) that may suggest inflammatory process at myocardium. 
      CONCLUSIONS: The patients diagnosed with DCM showed an arrhythmogenic phenotype 
      as well as SCD at young age supporting the recently proposed concept of 
      arrhythmogenic cardiomyopathy. This study also demonstrates relatively low 
      penetrance of truncating DSP variant in the probands' family members by the age 
      of 40. Further studies are needed to elucidate the possible relations between 
      myocardial inflammation and pathogenic DSP variants.
FAU - Helio, Krista
AU  - Helio K
AUID- ORCID: 0000-0001-6244-1969
AD  - Heart and Lung Center, Helsinki University Hospital, University of Helsinki, 
      Helsinki, Finland. krista.helio@helsinki.fi.
FAU - Kangas-Kontio, Tiia
AU  - Kangas-Kontio T
AD  - Blueprint Genetics, Helsinki, Finland.
FAU - Weckstrom, Sini
AU  - Weckstrom S
AD  - Heart and Lung Center, Helsinki University Hospital, University of Helsinki, 
      Helsinki, Finland.
FAU - Vanninen, Sari U M
AU  - Vanninen SUM
AD  - Heart Center, Tampere University Hospital, Tampere, Finland.
FAU - Aalto-Setala, Katriina
AU  - Aalto-Setala K
AD  - Heart Center, Tampere University Hospital, Tampere, Finland.
AD  - Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
FAU - Alastalo, Tero-Pekka
AU  - Alastalo TP
AD  - Blueprint Genetics, Helsinki, Finland.
FAU - Myllykangas, Samuel
AU  - Myllykangas S
AD  - Blueprint Genetics, Helsinki, Finland.
FAU - Helio, Tiina M
AU  - Helio TM
AD  - Heart and Lung Center, Helsinki University Hospital, University of Helsinki, 
      Helsinki, Finland.
FAU - Koskenvuo, Juha W
AU  - Koskenvuo JW
AD  - Blueprint Genetics, Helsinki, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200131
PL  - England
TA  - BMC Med Genet
JT  - BMC medical genetics
JID - 100968552
RN  - 0 (Contrast Media)
RN  - 0 (Desmoplakins)
RN  - AU0V1LM3JT (Gadolinium)
RN  - Familial dilated cardiomyopathy
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Aged, 80 and over
MH  - Arrhythmogenic Right Ventricular Dysplasia/diagnostic 
      imaging/*genetics/physiopathology
MH  - Cardiomyopathy, Dilated/diagnostic imaging/*genetics/physiopathology
MH  - Contrast Media/administration & dosage
MH  - Desmoplakins/*genetics
MH  - Female
MH  - Gadolinium/administration & dosage
MH  - *Genetic Predisposition to Disease
MH  - Heart Ventricles/physiopathology
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Pedigree
MH  - Penetrance
MH  - Ventricular Dysfunction, Left/diagnostic imaging/genetics/physiopathology
PMC - PMC6995042
OTO - NOTNLM
OT  - Arrhythmogenic cardiomyopathy
OT  - Cardiomyopathies
OT  - DSP
OT  - Dilated cardiomyopathy
OT  - Mutation
OT  - desmoplakin
COIS- Minor conflict of interest: TPA, SM, JK are co-founders and TKK, TPA, SM, JK are 
      full-time employees of Blueprint Genetics, which offers genetic diagnostic 
      services.
EDAT- 2020/02/02 06:00
MHDA- 2020/03/04 06:00
PMCR- 2020/01/31
CRDT- 2020/02/02 06:00
PHST- 2019/07/03 00:00 [received]
PHST- 2020/01/20 00:00 [accepted]
PHST- 2020/02/02 06:00 [entrez]
PHST- 2020/02/02 06:00 [pubmed]
PHST- 2020/03/04 06:00 [medline]
PHST- 2020/01/31 00:00 [pmc-release]
AID - 10.1186/s12881-020-0955-z [pii]
AID - 955 [pii]
AID - 10.1186/s12881-020-0955-z [doi]
PST - epublish
SO  - BMC Med Genet. 2020 Jan 31;21(1):19. doi: 10.1186/s12881-020-0955-z.