Molecular insight into heart development and congenital heart disease: An update review from the Arab countries

Aburawi, Elhadi H; Aburawi, Hanan E.; Bagnall, K. M.; Bhuiyan, Zahurul A.

doi:10.1016/j.tcm.2014.11.007

Cited by 17 publications

(13 citation statements)

References 108 publications

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“…If proper precautionary measures are not taken, these defects will be predisposed to late complications and ultimately cause a decrease in life expectancy [ 26 ]. This is frequently life threatening and can cause a profound economic and social burden on patients and their family [ 27 ]. The screening of genetic factors associated with CHD is important in clinical practice because it can improve genetic counseling by identifying patients with pathogenic mutations which are related to further cardiac complications and can be transmitted to offspring.…”

Section: Discussionmentioning

confidence: 99%

A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease

Zhang¹,

Wang²,

Wang³

et al. 2016

PLoS ONE

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BackgroundCongenital heart disease (CHD) is the most prevalent type of birth defect in human, with high morbidity in infant. Several genes essential for heart development have been identified. GATA4 is a pivotal transcription factor that can regulate the cardiac development. Many GATA4 mutations have been identified in patients with different types of CHD.AimsIn this study, the NKX2-5, HAND1 and GATA4 coding regions were sequenced in a family spanning three generations in which seven patients had CHD. Disease-causing potential variation in this family was evaluated by bioinformatics programs and the transcriptional activity of mutant protein was analyzed by the dual luciferase reporter assay.ResultsA novel GATA4 mutation, c.C931T (p.R311W), was identified and co-segregated with the affected patients in this family. The bioinformatics programs predicted this heterozygous mutation to be deleterious and the cross-species alignment of GATA4 sequences showed that the mutation occurred within a highly conserved amino acid. Even though it resided in the nuclear localization signal domain, the mutant protein didn’t alter its intracellular distribution. Nevertheless, further luciferase reporter assay demonstrated that the p.R311W mutation reduced the ability of GATA4 to activate its downstream target gene.ConclusionsOur study identified a novel mutation in GATA4 that likely contributed to the CHD in this family. This finding expanded the spectrum of GATA4 mutations and underscored the pathogenic correlation between GATA4 mutations and CHD.

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Section: Discussionmentioning

confidence: 99%

A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease

Zhang¹,

Wang²,

Wang³

et al. 2016

PLoS ONE

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“…In a four-chamber heart, FHF-derived cells give rise to the left ventricle as well as parts of the atrial chambers. SHF-derived cells contribute to the main parts of the atrial tissue, the right ventricle, and the outflow tract (OFT) [ 1 , 2 , 3 , 5 , 6 ]. Embryonic cardiomyocytes continuously undergo hyperplastic growth and maturation.…”

Section: Contemporary Understanding Of Heart Developmentmentioning

confidence: 99%

Functions of miRNAs during Mammalian Heart Development

Yan

Jiao

2016

IJMS

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MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest cells. Recent data have identified various miRNAs as critical regulators of the proper differentiation, proliferation, and survival of these cell types. In this review, we briefly introduce the contemporary understanding of mammalian cardiac development. We also focus on recent developments in the field of cardiac miRNAs and their functions during the development of different cell types.

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“…In this study, we have explored the genetic basis of CM in the population of Qatar through the establishment of The Dilated cardiomyopathy, Obstructive‐Hypertrophic cardiomyopathy and Arrhythmogenic right ventricular cardiomyopathy Registry (The DOHA‐Registry) and Biobank at the Heart Hospital in Qatar, followed by genetic testing for the registry participants. The study took into account unique features of the population of Qatar, including the high level of consanguinity estimated at 54% (Bener & Alali, 2006 ) which increases the burden of recessively inherited diseases including heart diseases (Aburawi et al, 2015 ). In addition, the endogamous nature of the populations living in Qatar, including Qataris, other Arab populations, and Southeast Asians, can lead to autozygosity of founder mutations, and thus helps revealing novel disease mutations and genes that are not detected in outbred populations (Maddirevula et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs

Al-Shafai

Alhashemi

Chidambaram³

et al. 2021

Molec Gen & Gen Med

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Background Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are serious inherited heart diseases with various causative mutations identified. The full spectrum of causative mutations remains to be discovered, especially in understudied populations. Methods Here, we established the DOHA Registry and Biobank for cardiomyopathies in Qatar, followed by sequencing of 174 genes on 51 HCM and 53 DCM patients, and 31 relatives. Results In HCM, the analysis of 25 HCM‐associated genes showed that 20% of HCM cases had putative pathogenic variants for cardiomyopathy, mainly in sarcomere genes. Additional 49% of HCM cases had variants of uncertain significance, while 31% of HCM cases had likely benign variant(s) or had no variants identified within the analyzed HCM genes. In DCM, 56 putative DCM genes were analyzed. Eight percent of DCM cases had putative pathogenic variants for DCM, in the TTN gene while 70% of cases had variants of uncertain significance, in the analyzed DCM genes, that will need further pathogenicity assessment. Moreover, 22% of DCM cases remain unexplained, by having likely benign variant(s) or having no variants detected in any of the analyzed DCM genes. Conclusion We identified or replicated at least four recurrent variants among cardiomyopathy patients, which could be founder disease mutations in the Arabic population, including a frameshift variant (c.1371_1381dupTATCCAGTTAT) of unknown significance in the FKTN gene which seems to cause DCM in homozygosity, and HCM in heterozygosity. In vivo and/or in vitro functional validation need to be pursued in order to assess the pathogenicity of the identified variants.

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Molecular insight into heart development and congenital heart disease: An update review from the Arab countries

Cited by 17 publications

References 108 publications

A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease

A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease

Functions of miRNAs during Mammalian Heart Development

Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs

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