Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 29;4(1):13-23.
doi: 10.1007/s43657-023-00126-w. eCollection 2024 Feb.

A Heterozygous Phospholamban Variant (p.R14del) Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy

Han Mo #  1 , Xiumeng Hua #  2 , Mengni Bao  1 , Zhe Sun  1 , Xiao Chen  2 , Mengda Xu  2 , Jiangping Song  1   2   3
Affiliations

A Heterozygous Phospholamban Variant (p.R14del) Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy

Han Mo et al. Phenomics. .

Abstract

This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) caused by pathogenic mutations in the Phospholamban (PLN) gene. The study included 170 patients who had a confirmed diagnosis of ARVC and underwent PLN genetic screening using next-generation sequencing. The findings of this study provide valuable insights into the association between PLN mutations and ARVC, which can aid in the development of more effective diagnostic and treatment strategies for ARVC patients. Out of the patients evaluated, six had a rare pathogenic mutation in PLN with the same p.R14del variant. Family screening revealed that heterozygous carriers of p.R14del exhibited a definite ARVC phenotype. In clinical studies, individuals with the p.R14del mutation experienced a similar rate of malignant arrhythmia events as those with classic desmosome mutations. After adjusting for covariates, individuals with PLN mutations had a two point one seven times greater likelihood of experiencing transplant-related risks compared to those who did not possess PLN mutations (95% CI 1.08-6.82, p = 0.035). The accumulation of left ventricular fat and fibers is a pathological marker for ARVC patients with p.R14del mutations. In a cohort of 170 Chinese ARVC patients, three point five percent of probands had the PLN pathogenic variant (p.R14del) and all were female. Our data shows that PLN-related ARVC patients are at high risk for ventricular arrhythmias and heart failure, which requires clinical differentiation from classic ARVC. Furthermore, carrying the p.R14del mutation can be an independent prognostic risk factor in ARVC patients.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-023-00126-w.

Keywords: Arrhythmogenic right ventricular cardiomyopathy; Heart failure; Left ventricular involvement; Phospholamban; Risk stratification.

PubMed Disclaimer

Conflict of interest statement

Conflict of interestThe authors have no conflicts of interest to declare in relation to this study.

Figures

Fig. 1
Fig. 1
Screening process and sequence results of PLN variant a NGS analysis pipeline diagram, fq fastq, QC quailty control, vcf the variant call format, bam binary alignment map, bqsr base quality score recalibration, vqsr variant quality score recalibration, b sanger sequence diagrams of six PLN probands, c family cascade screening of proband 1
Fig. 2
Fig. 2
Analysis of pathological features of transplant patients a Masson map of six site pathology of transplant patients. The top arrow indicates fibrosis and the bottom arrow indicates fatty infiltration. b Qualitative pathological analysis was used to quantify the degree of fibrosis and adipose invasion at different sites (LV, IVS, and RV) in PLN transplant patients. c–e Comparison of fat, fibrosis and Myocardium proportions at different sites (LV, IVS and RV) in patients carrying different variants (PLN, PKP2, DSG2 and NV-HT). *p < 0.05; **p < 0.01
Fig. 3
Fig. 3
Survival analysis a From birth to endpoint follow-up, with the endpoint being MACE events. b From diagnosis of ARVC to endpoint follow-up, with the endpoint being HT
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Bhonsale A, Te Riele A, Sawant AC, et al. Cardiac phenotype and long-term prognosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia patients with late presentation. Heart Rhythm. 2017;14(6):883–891. doi: 10.1016/j.hrthm.2017.02.013. - DOI - PubMed
    1. Calkins H, Corrado D, Marcus F. Risk stratification in arrhythmogenic right ventricular cardiomyopathy. Circulation. 2017;136(21):2068–2082. doi: 10.1161/CIRCULATIONAHA.117.030792. - DOI - PMC - PubMed
    1. Castanos Gutierrez SL, Kamel IR, Zimmerman SL. current concepts on diagnosis and prognosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia. J Thorac Imaging. 2016;31(6):324–335. doi: 10.1097/RTI.0000000000000171. - DOI - PubMed
    1. Chen K, Rao M, Guo G, et al. Recessive variants in plakophilin-2 contributes to early-onset arrhythmogenic cardiomyopathy with severe heart failure. Europace. 2019;21(6):970–977. doi: 10.1093/europace/euz026. - DOI - PubMed
    1. Chen L, Rao M, Chen X, et al. A founder homozygous DSG2 variant in East Asia results in ARVC with full penetrance and heart failure phenotype. Int J Cardiol. 2019;274:263–270. doi: 10.1016/j.ijcard.2018.06.105. - DOI - PubMed

LinkOut - more resources