RCAN1 Mutation and Functional Characterization in Children with Sporadic Congenital Heart Disease

Overview

Journal Pediatr Cardiol

Specialties Cardiology & Vascular Diseases
Pediatrics

Date 2017 Oct 11

PMID 28993896

Citations 6

Authors

Xiaoyong Li

Lei Shi

Ming Xu

Xun Zheng

Yiwen Yu

Jing Jin

Affiliations

Soon will be listed here.

Abstract

Congenital heart disease (CHD) is the most frequent birth defect. RCAN1 (regulator of calcineurin 1) contributes to CHD in Down syndrome. However, whether RCAN1 is also associated with nonsyndromic CHD remains unclear. This study sequenced the exons and flanking region of RCAN1 in 128 sporadic CHD patients and 150 normal controls. We identified six novel heterozygous mutations in CHD patients. Functional assay showed that the g.482G>T could obviously raise the promoter activity of RCAN1.4 in vitro; However, we failed to detect the expression of RCAN1 in the right auricle, which made it confused to evaluate the pathogenicity of this mutation. In addition, we demonstrated that c.290T>C and g.1056+58C>A had no effect on the alternative splicing of RCAN1. The *196C>T, *790G>A, and *1278C>G did not influence the translation of RCAN1 post transcription. In conclusion, a novel mutation of g.482G>T in RCAN1 may be related to CHD by causing overexpression of RCAN1.4.

Citing Articles

Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects.

Mehta Z, Touma M Int J Mol Sci. 2023; 24(2).

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RCAN1 deficiency aggravates sepsis-induced cardiac remodeling and dysfunction by accelerating mitochondrial pathological fission.

Zhuang J, Chen L, Li G, Xia L, Wu S, Leng J Inflamm Res. 2022; 71(12):1589-1602.

PMID: 36305917 DOI: 10.1007/s00011-022-01628-5.

RCAN1 in cardiovascular diseases: molecular mechanisms and a potential therapeutic target.

Wang S, Wang Y, Qiu K, Zhu J, Wu Y Mol Med. 2020; 26(1):118.

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Overexpression of in the Developing Heart Causes Valvar and Contractility Defects: Implications for Human Congenital Heart Disease.

Akasaka T, Ocorr K, Lin L, Vogler G, Bodmer R, Grossfeld P J Cardiovasc Dev Dis. 2020; 7(2).

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ISL1 loss-of-function mutation contributes to congenital heart defects.

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