GATA4 molecular screening and assessment of environmental risk factors in a Moroccan cohort with tetralogy of Fallot

Bouchikhi, Ihssane El; Belhassan, Khadija; Moufid, Fatima Zohra; Houssaini, Mohammed Iraqui; Bouguenouch, Laila; Samri, Imane; Ouldim, Karim; Atmani, S.

doi:10.4314/ahs.v18i4.11

Cited by 8 publications

(5 citation statements)

References 34 publications

(38 reference statements)

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“…For this reason, in the present work, the NKX2.5 gene was chosen to be screened in a group of thirty-one patients with non-syndromic tetralogy of Fallot. This cohort has been screened for GATA4 mutations in an earlier paper [25], but no confirmed pathogenic mutation was revealed. Clinical and environmental investigation findings were discussed in that study and have shown a strong association between TOF occurrence and maternal passive smoking.…”

Section: Discussionmentioning

confidence: 99%

Screening of NKX2.5 gene in Moroccan Tetralogy of Fallot (TOF) patients: worldwide mutation rate comparisons show a significant association between R25C variant and TOF phenotype

Bouchikhi

Belhassan

Moufid

et al. 2021

Egypt J Med Hum Genet

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Background Tetralogy of Fallot is the most prevalent cyanotic congenital heart disease, occurring in 1/3 600 live births. This disorder comprises ventricular septal defect, right ventricular outflow obstruction, over-riding aorta, and right ventricular hypertrophy. The present study aims to reveal the spectrum of Nk2 homeobox 5 (NKX2-5) variants identified in a Moroccan non-syndromic tetralogy of Fallot cohort and to compare mutation rate with different studies from all over the world. Thirty-one patients with non-syndromic tetralogy of Fallot were recruited in this cross-sectional study. DNAs were extracted, and coding regions of NKX2.5 were PCR-amplified and sequenced. The obtained sequences were analyzed using different bioinformatics tools. Statistical comparisons were carried out using the R software. Results R25C mutation was found in two patients, in association with the E21E variant. The latter variant was frequently observed in the population and seems to have a potential altering effect on the splicing process. The NKX2.5 mutation rate in our tetralogy of Fallot population is around 6.4%, and no significant difference was noticed in comparison with previous studies. At the same time, a comparison of R25C mutation rate between atrial septal defect and tetralogy of Fallot worldwide populations shows a particular association of R25C mutation with tetralogy of Fallot phenotype. Conclusions This study reveals a consistency between our NKX2.5 mutation rate and those of different tetralogy of Fallot populations around the world. Our findings suggest a possible combined effect of R25C mutation and E21E variant on the carriers and emphasize particularly the significant association of R25C mutation with tetralogy of Fallot, which highlights the importance of an anticipative screening for TOF phenotype among the carriers’ offspring at the perinatal period.

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Section: Discussionmentioning

confidence: 99%

Screening of NKX2.5 gene in Moroccan Tetralogy of Fallot (TOF) patients: worldwide mutation rate comparisons show a significant association between R25C variant and TOF phenotype

Bouchikhi

Belhassan

Moufid

et al. 2021

Egypt J Med Hum Genet

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“…In addition to the CNV mechanism, there are other types of genetic mutations that may cause PA. For example, mutations in NKX2-5, GATA4 and TBX5 genes can cause conotruncal defects and are intricately associated with PA (31)(32)(33). In addition to these common genes, other important regulatory genes, such as NOTCH1 have recently been reported to be closely related to PA as revealed in Genome wide association study analysis of TOF whole exome sequencing data (23).…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Dihydrofolate Reductase Gene Knock-In Zebrafish Strain to Aid Preliminary Analysis of Congenital Heart Disease Mechanisms

Gong

Xie

Yang

et al. 2021

Front. Cardiovasc. Med.

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Background: The dihydrofolate reductase (DHFR) gene is imperative in development, therefore it is essential to explore its effects on heart development. Thus, here a dhfr zebrafish knock-in (KI) strain was constructed.Methods: CRISPR/Cas9 technology was used to establish the dhfr KI zebrafish strain. This strain was hybridized with TgG fluorescent strain zebrafish to observe the phenotypes of heart shape, size, and circularization direction. Wild-type (WT) and KI zebrafish were then dissected and histologically stained to observe pathological changes. Western blot analysis was used to verify the increased expressions of zebrafish genes after KI. Hybridization experiments were used to confirm the presence of abnormal gonadal dysplasia.Results: The zebrafish dhfr KI strain was successfully constructed through CRISPR/Cas9 technology. At 6 days post fertilization (dpf), microscopic examinations of KI (homozygous) specimens revealed pericardial effusions, heart compressions, and curled tails. Compared with WT, the Hematoxylin and Eosin (H&E) tissue sections of KI-homozygous zebrafish showed defects such as reduced atria and ventricles. Western blot analysis indicated that the expression of the DHFR protein increased in both heterozygotes and homozygotes of dhfr KI zebrafish. Hybridization experiments revealed that dhfr KI may affect gonadal function.Conclusion: The DHFR gene plays an important regulatory role in the process of heart development, and copy number variations (CNVs) of this gene may constitute a new pathogenic mechanism of congenital heart disease (CHD).

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“…However, a British population-based study found no evidence for an association between advanced maternal age and the risk of CHD [9]. In addition, studies conducted in Morocco and Iran found no association between previous unfavorable fetal outcomes and the risk of CHD [10,11]. Previous studies have examined the impact of sociodemographic factors on the risk of CHD in other countries, but to our knowledge, no study has examined the role of sociodemographic factors on the risk of CHD between infants with CHD and healthy controls in the US.…”

Section: Introductionmentioning

confidence: 98%

Sociodemographic Profile Associated with Congenital Heart Disease among Infants Less than 1 Year Old

Tran

Miner

Merkel

et al. 2023

Preprint

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Background: Congenital heart disease (CHD) affects thousands of newborns each year in the United States (US). Infants born with CHD have an increased risk of adverse health outcomes compared to healthy infants. These outcomes include, but are not limited to, neurodevelopmental, surgical, and mortality-related outcomes. Previous US-based research has explored how sociodemographic factors may impact these health outcomes in infants with CHD; however, their impact on the risk of CHD is unclear. This study aims to explore the sociodemographic profile related to CHD to help address health disparities that arise from race and social determinants of health. Defining the sociodemographic factors associated with CHD will encourage policy change and the implementation of preventative measures. Methods: This study is a secondary analysis of longitudinally collected data. We compared infants with CHD and healthy controls. We used a questionnaire to collect sociodemographic data. Pearson’s chi-square test/Fisher’s exact tests analyzed the associations among different sociodemographic factors between infants with CHD and healthy controls. Results: We obtained sociodemographic factors from 30 healthy control infants and 39 infants with CHD. We found a statistically significant difference in maternal education between our 2 groups of infants (p=0.004). Conclusion: Maternal education is associated with CHD. Future studies are needed to further characterize sociodemographic factors that may predict and impact the risk of CHD and to determine possible interventions that may help decrease health disparities regarding the risk of CHD.

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GATA4 molecular screening and assessment of environmental risk factors in a Moroccan cohort with tetralogy of Fallot

Cited by 8 publications

References 34 publications

Screening of NKX2.5 gene in Moroccan Tetralogy of Fallot (TOF) patients: worldwide mutation rate comparisons show a significant association between R25C variant and TOF phenotype

Screening of NKX2.5 gene in Moroccan Tetralogy of Fallot (TOF) patients: worldwide mutation rate comparisons show a significant association between R25C variant and TOF phenotype

Establishment of a Dihydrofolate Reductase Gene Knock-In Zebrafish Strain to Aid Preliminary Analysis of Congenital Heart Disease Mechanisms

Sociodemographic Profile Associated with Congenital Heart Disease among Infants Less than 1 Year Old

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