TY - JOUR
T1 - Buccal mucosa cells as a potential diagnostic tool to study onset and progression of arrhythmogenic cardiomyopathy
AU - Driessen, Helen E.
AU - van der Voorn, Stephanie M.
AU - Bourfiss, Mimount
AU - van Lint, Freyja H. M.
AU - Mirzad, Ferogh
AU - el Onsri, Laila
AU - Vos, Marc A.
AU - van Veen, Toon A. B.
N1 - Funding Information: Funding: This work was supported by The Netherlands Cardio Vascular Research Initiative (CVON): the Dutch Heart Foundation, Dutch Federation of University Medical Center, the Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences (CVON-eDETECT 2015-12, S.M.v.d.V., T.A.B.v.V.). Additional support was obtained from ‘Stichting Vriendenloterij’. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - In arrhythmogenic cardiomyopathy (ACM) pathogenic variants are found in genes encoding desmosomal proteins and in non-desmosomal genes, such as phospholamban (PLN, p.Arg14del variant). Previous research showed that plakoglobin protein levels and localization in the cardiac tissue of ACM patients, and PLN p.Arg14del patients diagnosed with an ACM phenotype, are disturbed. Moreover, the effects of pathogenic variants in desmosomal genes are reflected in non-cardiac tissues like buccal mucosa cells (BMC) which could serve as a promising new and non-invasive tool to support diagnosis. We collected the BMC of 33 ACM patients, 17 PLN p.Arg14del patients and 34 controls, labelled the BMC with anti-plakoglobin antibodies at different concentrations, and scored their membrane labelling. We found that plakoglobin protein levels were significantly reduced in BMC obtained from diagnosed ACM patients and preclinical variant carriers when compared to controls. This effect was independent from age and sex. Moderate to strong correlations were found with the revised 2010 Task Force Criteria score which is commonly used for ACM diagnosis (rs = −0.67, n = 64, p < 0.0001 and rs = −0.71, n = 64, p < 0.0001). In contrast, plakoglobin scores in PLN p.Arg14del patients were comparable to controls (p > 0.209), which suggests differences in underlying etiology. However, for the individual diagnosis of the ‘classical’ ACM patient, this method might not be discriminative enough to distinguish true patients from variant carriers and controls, because of the high interindividual variability.
AB - In arrhythmogenic cardiomyopathy (ACM) pathogenic variants are found in genes encoding desmosomal proteins and in non-desmosomal genes, such as phospholamban (PLN, p.Arg14del variant). Previous research showed that plakoglobin protein levels and localization in the cardiac tissue of ACM patients, and PLN p.Arg14del patients diagnosed with an ACM phenotype, are disturbed. Moreover, the effects of pathogenic variants in desmosomal genes are reflected in non-cardiac tissues like buccal mucosa cells (BMC) which could serve as a promising new and non-invasive tool to support diagnosis. We collected the BMC of 33 ACM patients, 17 PLN p.Arg14del patients and 34 controls, labelled the BMC with anti-plakoglobin antibodies at different concentrations, and scored their membrane labelling. We found that plakoglobin protein levels were significantly reduced in BMC obtained from diagnosed ACM patients and preclinical variant carriers when compared to controls. This effect was independent from age and sex. Moderate to strong correlations were found with the revised 2010 Task Force Criteria score which is commonly used for ACM diagnosis (rs = −0.67, n = 64, p < 0.0001 and rs = −0.71, n = 64, p < 0.0001). In contrast, plakoglobin scores in PLN p.Arg14del patients were comparable to controls (p > 0.209), which suggests differences in underlying etiology. However, for the individual diagnosis of the ‘classical’ ACM patient, this method might not be discriminative enough to distinguish true patients from variant carriers and controls, because of the high interindividual variability.
KW - Arrhythmogenic cardiomyopathy
KW - Buccal mucosa
KW - Diagnosis
KW - Phospholamban
KW - Plakoglobin
UR - http://www.scopus.com/inward/record.url?scp=85121363385&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms23010057
DO - https://doi.org/10.3390/ijms23010057
M3 - Article
C2 - 35008484
SN - 1661-6596
VL - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 1
M1 - 57
ER -