Whole-Exome Sequencing Identified a De Novo Mutation of<i> Junction Plakoglobin</i> (p.R577C) in a Chinese Patient with Arrhythmogenic Right Ventricular Cardiomyopathy

Liu, Lv; Chen, Chan; Li, Yali; Yu, Rong

doi:10.1155/2019/9103860

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…In the literature, a homozygous missense mutation was identified in the JUP gene by whole-exome sequencing in a case with only ARVC findings without accompanying cutaneous problems. 14 Therefore, cardiac MRI and ECHO were performed to exclude the ARVC, and normal findings were observed. The patient's 26-year-old brother, who was asymptomatic and did not receive any treatment, had only a homozygous variant in the JUP gene.…”

Section: Discussionmentioning

confidence: 99%

Molecular Approach of Hereditary Arrhythmias, Long QT Syndrome, and Arrhythmogenic Right Ventricular Cardiomyopathy

Saat¹,

Şahin²,

Erdem³

et al. 2022

Anatolian J Cardiol

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Background: Hereditary cardiac arrhythmias result from mutations in various genes encoding ion channels. One major channelopathy is long QT syndrome, which has excellent genetic and clinical heterogeneity. Arrhythmogenic right ventricular cardiomyopathy, another hereditary arrhythmia type, also shows high genetic heterogeneity and variable expressivity. Next-generation sequencing is an effective tool to reveal the disease’s underlying genetic etiology. Methods: In this study, we performed clinical exome sequencing or gene panel including cardiac arrhythmia and cardiomyopathy-associated genes by next-generation sequencing in 13 unrelated patients. Results: Five pathogenic or likely pathogenic mutations, including three novel mutations, were found in the total cases. Conclusion: This research shows a strong genetic heterogeneity in the disease. In addition, the study revealed that patients with QT interval prolongation on electrocardiogram might also have mutations in genes that are not associated with long QT syndrome, such as MYLK2 and DSG2. Therefore, our data helped expand the molecular scope of long QT syndrome. It is necessary to study with a broad perspective to elucidate the underlying molecular etiology in patients with hereditary cardiac arrhythmias.

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Section: Discussionmentioning

confidence: 99%

Molecular Approach of Hereditary Arrhythmias, Long QT Syndrome, and Arrhythmogenic Right Ventricular Cardiomyopathy

Saat¹,

Şahin²,

Erdem³

et al. 2022

Anatolian J Cardiol

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“…Variant validation and cosegregation analysis were performed on each member by Sanger sequencing with the following primers of MITF (NT_022495, NM_000248, and NP_000239) and designed by Primer3: 5-′TTCCGTTGTCATGACCTGGA-3′ and 5-′AACACGCGATTGTACTCACG-3′. The candidate variant was also examined in 200 healthy adults of both sexes and different ages, who were enrolled by ourselves and to be used as an internal control for genetic variants potentially specific for the Han Chinese [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

MITF p.Arg217Thr Variant Identified in a Han Chinese Family with Tietz/Waardenburg Syndrome

Liu

et al. 2021

BioMed Research International

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Waardenburg syndrome (WS) is a group of rare genetic disorders characterized by hearing loss, changes in coloring of hair, skin, and eyes, and alterations in the shape of the face. Tietz syndrome is another rare disorder which presented similar phenotypes to WS. Patients with Tietz/Waardenburg syndrome often present with pale blue eyes, albino skin, and distinctive hair coloring, such as a patch of white hair or hair that prematurely turns gray. At present, more than six candidate genes are responsible for four types of Waardenburg syndrome and Tietz syndrome. This study is aimed at identifying the pathogenic gene variants in a three-generation Han Chinese family with hearing loss, blue-gray iris, albino skin, and white hair. In order to discover the molecular genetic lesion underlying the disease phenotype, whole exome sequencing in the proband, with Tietz/Waardenburg syndrome phenotypes, of a Han Chinese family from HeBei, China, was conducted. A novel heterozygous c.650G>C/p.Arg217Thr variant in melanocyte inducing transcription factor (MITF) was identified. Sanger sequencing further validated that this mutation existed in three affected individuals and absent in healthy family members. Bioinformatics analysis predicted that this mutation was deleterious. Our study further identified the genetic lesion of the family. Simultaneously, our study may also contribute to genetic counseling, embryonic screening of in vitro fertilized embryos, and prenatal genetic diagnosis of patients with Tietz/Waardenburg syndrome, especially for the proband, unmarried and unpregnant women, to reduce familial transmission in this Han Chinese family.

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“…Soon after the identification of JUP as an ACM-causing gene, Carvajal syndrome was found to be underlied by a deletion in the desmoplakin gene ( DSP ), coding for another desmosomal protein [ 10 ]. Since these early discoveries, more mutations were identified in JUP and DSP in ACM patients showing dominantly inherited forms of the disease [ 11 , 12 , 13 , 14 , 15 ]. Desmosomes are sites of cell–cell coupling.…”

Section: Genetics Of Acmmentioning

confidence: 99%

Cheek-Pro-Heart: What Can the Buccal Mucosa Do for Arrhythmogenic Cardiomyopathy?

Bueno-Betí

Asimaki

2023

Biomedicines

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Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease associated with ventricular arrhythmias and a high risk of sudden cardiac death (SCD). Although the disease was described over 40 years ago, its diagnosis is still difficult. Several studies have identified a set of five proteins (plakoglobin, Cx43, Nav1.5, SAP97 and GSK3β), which are consistently re-distributed in myocardial samples from ACM patients. Not all protein shifts are specific to ACM, but their combination has provided us with a molecular signature for the disease, which has greatly aided post-mortem diagnosis of SCD victims. The use of this signature, however, was heretofore restricted in living patients, as the analysis requires a heart sample. Recent studies have shown that buccal cells behave similarly to the heart in terms of protein re-localization. Protein shifts are associated with disease onset, deterioration and favorable response to anti-arrhythmic therapy. Accordingly, buccal cells can be used as a surrogate for the myocardium to aid diagnosis, risk stratification and even monitor response to pharmaceutical interventions. Buccal cells can also be kept in culture, hence providing an ex vivo model from the patient, which can offer insights into the mechanisms of disease pathogenesis, including drug response. This review summarizes how the cheek can aid the heart in the battle against ACM.

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Whole-Exome Sequencing Identified a De Novo Mutation of Junction Plakoglobin (p.R577C) in a Chinese Patient with Arrhythmogenic Right Ventricular Cardiomyopathy

Cited by 8 publications

References 29 publications

Molecular Approach of Hereditary Arrhythmias, Long QT Syndrome, and Arrhythmogenic Right Ventricular Cardiomyopathy

Molecular Approach of Hereditary Arrhythmias, Long QT Syndrome, and Arrhythmogenic Right Ventricular Cardiomyopathy

MITF p.Arg217Thr Variant Identified in a Han Chinese Family with Tietz/Waardenburg Syndrome

Cheek-Pro-Heart: What Can the Buccal Mucosa Do for Arrhythmogenic Cardiomyopathy?

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