CASQ2 variants in Chinese children with catecholaminergic polymorphic ventricular tachycardia

Abstract

BackgroundBiallelic variants of the CASQ2 are known to cause the autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disease that predisposes young individuals to syncope and sudden cardiac death. To date, only about 24 CASQ2 variants have been reported in association with CPVT pathogenesis; furthermore, studies in Asians, especially in the Chinese population, are relatively rare. The aim of this study was to detect CASQ2 variants in Chinese patients with CPVT.MethodsWe used targeted next‐generation sequencing (NGS) to identify CASQ2 variants in Chinese patients with CPVT. A screening process was performed to prioritize rare variants of potential functional significance. Sanger sequencing was conducted to conform the candidate variants and determine the parental origin.ResultsWe identified seven different CASQ2 variants, of which three (c.1074_1075delinsC, c.1175_1178delACAG, and c.838+1G>A) have not been previously reported. The variants exhibited autosomal recessive inheritance, and were detected in four unrelated Chinese families with CPVT. They included a nonsense variant c.97C>T (p.R33*) and a missense variant c.748C>T (p.R250C) in Family 1 with three CPVT patients; two heterozygous frameshift variants, c.1074_1075delinsC (p.G359Afs*12) and c.1175_1178delACAG (p.D392Vfs*84), in Family 2 with one CPVT patient; one pathogenic homozygous variant c.98G>A (p.R33Q) of CASQ2 in the CPVT patient of Family 3; and two heterozygous splicing variants, (c.532+1G>A) and (c.838+1G>A), in Family 4 with one CPVT patient.ConclusionTo our knowledge, this is the first systematic study of Chinese children with CASQ2 variants. Our work further expands the genetic spectrum of CASQ2‐associated CPVT.

Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

“…Of note, CDK1 and KPNA2 were significantly upregulated in the Oncomine meta-analysis and thus were in line with our TCGA-BLCA analysis, while TPM1 was unaltered in the meta-analysis but significantly downregulated in our analysis ( Figure 5). CASQ2 seems to play a role in catecholaminergic polymorphic ventricular tachycardia research [57]. CRYAB was involved in a variety of signaling pathways implicated in breast cancer, lung cancer, prostate cancer, and ovarian cancer [58].…”

Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: A Translational Perspective for the Clinician-Scientist

“…A newly devised "phenotype-enhanced" scoring system for RYR2 variants has recently been described, which factors the pre-test probability of CPVT into the assignment of pathogenicity [95]. In addition, more than 24 pathogenic CASQ2 variants associated with CPVT have been identified to date [79]. Consanguineous family members are typically tested for CASQ2 variants.…”

Clinical Characteristics, Genetic Findings and Arrhythmic Outcomes of Patients with Catecholaminergic Polymorphic Ventricular Tachycardia from China

“…A systematic search of the PubMed and MedRvix databases yielded 1049 and 12 articles, respectively. After the exclusion of overlapping cohorts, a total of 56 unique cases from six cities by 11 studies were included [11,25,[32][33][34][35][36][37][38][39][40]. Their clinical characteristics and test results are shown in Table 1.…”

“…Of these, catecholaminergic ventricular tachycardia (CPVT) is a less prevalent condition compared to Brugada syndrome (BrS) in Asia [7,8]. It is typically caused by mutations in either the ryanodine receptor 2 (RyR2) [9] or the calsequestrin 2 (CASQ2) [10,11], but mutations in other genes such as calmodulin (CALM) have been implicated [12][13][14]. CPVT is usually precipitated by exercise or distress, which results in bidirectional VT, presenting in the first two decades of life [15].…”

“…Another Japanese reported on the findings of 29 patients [23]. However, to date, case descriptions from China have been limited to case series [11,[24][25][26] and there is no established registry nationally. Moreover, many of these reports were also published in Chinese, and have limited accessibility to researchers beyond the country.…”