![handle is hein.journals/injlegame129 and id is 1 raw text is: Int J Legal Med (2015) 129:1-10
DOI 10.1007/s00414-014-0996-y
ORIiINAL,\RTI(2ATLE
Sequenom MassARRAY approach in the arrhythmogenic right
ventricular cardiomyopathy post-mortem setting: clinical
and forensic implications
M. Alcalde - O. Campuzano - C. Allegue - M. Torres-
E. Arbelo - S. Partemi - A. Iglesias - J. Brugada-
A. Oliva - A. Carracedo - R. Brugada
Received: 8 February 2014 /Accepted: 16 April 2014 /Published online: 16 May 2014
C Springer-Verlag Berlin Heidelberg 2014
Abstract Arrhythmogenic right ventricular cardiomyopathy
(ARVC) is a rare cardiac disease characterized by myocardial
fibrofatty replacement, which can lead to sudden death.
Previous studies have described a reduction of plakoglobin
(PKG) protein at the level of intercalated disks as the hallmark
of ARVC. The main objective of this study was to investigate
the involvement of desmosome mutations in the histological
phenotype of ARVC. We performed a genetic analysis of
ARVC cases, and histological characterization of ARVC heart
tissue samples. We genetically analyzed 48 ARVC cases
distributed into two groups: 42 human tissue heart samples
with conclusive diagnoses of ARVC after post-mortem exam-
ination; and six DNA samples from peripheral blood of living
patients who were clinically diagnosed. Sequenom
M. Alcalde O. Campuzano - C. Allegue - A. Iglesias - R. Brugada
Cardiovascular Genetics Center, University of Girona-IDIBGI,
Girona, Spain
M. Torres - A. Carracedo
Grupo de Medicina Xen6mica- Centro Nacional de Genotipado
(CEGEN-ISCIII)- Instituto de Ciencias Forenses-Universidade, de
Santiago de Compostela, Spain
E. Arbelo - J. Brugada
Unitat Aritmies, Hospital Clinic, Universitat de Barcelona,
Barcelona, Spain
S. Partemi - A. Oliva
Institute of Legal Medicine, Catholic University, Rome, Italy
A. Carracedo
Center of Excellence in Genomic Medicine Research, King
Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
R. Brugada (E )
School of Medicine, Cardiovascular Genetics Center, Girona, C/Pic
de Peguera 11, 17003 Girona, Spain
e-mail: ramon@brugada.org
MassARRAY analysis revealed three ARVC-associated vari-
ants in three patients in 42 tissue samples (7.14 %). Three
individuals carried one single pathogenic mutation, p.R811S
_PKP2, p.S824LDSC2, and p.T526M_PKP2 in postmortem
samples. In the living patients group, Sequenom MassARRA
Y revealed no mutation, however, later Sanger sequencing
analysis identified three ARVC mutations in 2/6 patients not
included in the Sequenom design. In post-mortem tissue sam-
ples we performed immunohistochemical labeling for desmo-
somal proteins and Connexin 43. This study revealed that
PKP2 carriers present either absent or clearly reduced PKG
immunolabeling, while the DSC2 carrier showed PKG
immunolabeling similar to control samples. Immunolabeling
for Cx43 did not show any differences compared to controls.
The present Sequenom MassARRAY design is a useful tool
for post-mortem genetic diagnosis of ARVC. Plakoglobin
reduction occurs at intercalated disks, while other desmosome
proteins and Cx43 remain unaltered.
Keywords Sudden cardiac death . ARVC - Genetics.
Plakoglobin - Cx43
Introduction
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is
a rare cardiac disease (ORPHA247) characterized by a pro-
gressive myocardial fibrofatty replacement, mainly of the
right ventricle (RV), although up to 50 % of patients also
show a left ventricular (LV) involvement [1]. This myocyte
substitution disrupts electrical transmission, causing ventricu-
lar arrhythmias and sudden cardiac death (SCD) [2, 3]. The
National Centre for Biotechnology Information (NCBI) estab-
lishes a wide range of prevalence (1/2500-1/5000), age (2-
70 years old) [4, 5], and differences in gender (3:1 in men) [6,
' Springer](ViewImageLocal?handle=hein.journals/injlegame129&div=1&collection=&method=preview&ext=.png&size=3)
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