Mutations ofZFPM2/FOG2 gene in sporadic cases of tetralogy of Fallot

Pizzuti, Antonio; Sárközy, Anna; Newton, Anthea L.; Conti, Emanuela; Flex, Elisabetta; Digilio, María Cristina; Amati, Francesca; Gianni, Debora; Tandoi, Caterina; Marino, Bruno; Crossley, Merlin; Dallapiccola, Bruno

doi:10.1002/humu.10261

Cited by 123 publications

(72 citation statements)

References 22 publications

(25 reference statements)

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“…In experimental gene targeting of ZFPM2/FOG2 in mice, the mutation resulted in cardiac malformation including TOF, endothelial specific disruption (DORV, a common AV valve), VSD and ASD as well as left ventricular wall hypoplasia, and the failure to form coronary arteries (Tevosian et al, 2000). Recent reports found mutations of the ZFPM2/FOG2 gene associated with TOF (De Luca et al, 2010;Pizzuti et al, 2003).  ZIC3, Zic family member 3 heterotaxy 1; This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins.…”

Section: Single Gene Disordermentioning

confidence: 99%

Epidemiology and Etiology of Congenital Heart Diseases

Sayasathid¹,

Sukonpan²,

Somboonna³

2012

Congenital Heart Disease - Selected Aspects

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Section: Single Gene Disordermentioning

confidence: 99%

Epidemiology and Etiology of Congenital Heart Diseases

Sayasathid¹,

Sukonpan²,

Somboonna³

2012

Congenital Heart Disease - Selected Aspects

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“…We used this new assay to analyze a cohort of non-syndromic patients with anatomic types of cardiac defects previously associated with GATA4 gene mutations. This cohort was mutation-negative for GA-TA4 [4][5][6][7][8][9][10][11]13,14], as well as for the NKX2.5 [5,7,[31][32][33] and FOG2 [34] genes, previously related to cardiac septal defects and/or conotruncal anomalies.…”

Section: Introductionmentioning

confidence: 99%

Multiplex Ligation-Dependent Probe Amplification Analysis ofGATA4Gene Copy Number Variations in Patients with Isolated Congenital Heart Disease

et al. 2010

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Abstract. GATA4 mutations are found in patients with different isolated congenital heart defects (CHDs), mostly cardiac septal defects and tetralogy of Fallot. In addition, GATA4 is supposed to be the responsible gene for the CHDs in the chromosomal 8p23 deletion syndrome, which is recognized as a malformation syndrome with clinical symptoms of facial anomalies, microcephaly, mental retardation, and congenital heart defects. Thus far, no study has been carried out to investigate the role of GATA4 copy number variations (CNVs) in non-syndromic CHDs. To explore the possible occurrence of GATA4 gene CNVs in isolated CHDs, we analyzed by multiplex ligation-dependent probe amplification (MLPA) a cohort of 161 non-syndromic patients with cardiac anomalies previously associated with GATA4 gene mutations. The patients were mutation-negative for GATA4, NKX2.5, and FOG2 genes after screening with denaturing high performance liquid chromatography. MLPA analysis revealed that normalized MLPA signals were all found within the normal range values for all exons in all patients, excluding a major contribution of GATA4 gene CNVs in CHD pathogenesis.

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“…Thus, differences in the enhancer sequence per se are unlikely to explain intersubject variation in constitutive CYP2E1 expression. Known functional genetic variants in the transcription factors binding within this region, such as GATA4 (Garg et al, 2003) and FTF (Nitta et al, 1999), or in cooperating cofactors, such as FOG2 (Pizzuti et al, 2003) and SHP (Nishigori et al, 2001), may contribute to intersubject variation in constitutive CYP2E1 expression. Furthermore, FTF and GATA4 are known to play pivotal roles in the differentiation and development of endodermally derived tissues, such as liver and intestine (Molkentin, 2000;Fayard et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Identification and Functional Analysis of a Novel HumanCYP2E1Far Upstream Enhancer

Shadley

Divakaran²,

Munson³

et al. 2007

Mol Pharmacol

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Both transcriptional and post-transcriptional CYP2E1 regulatory mechanisms are known, resulting in 20-fold or greater variation in CYP2E1 expression. To evaluate functional regulatory elements controlling transcription, CYP2E1 promoter constructs were used to make adenovirus vectors containing CYP2E1 promoter-driven luciferase reporters for analyses in both primary human hepatocytes and HepG2 cells. A 1.2-kilobase pair portion of the CYP2E1 promoter was associated with 5-to 10-fold greater luciferase activity. This upstream region contained five direct repeats of 59 base pairs (bp) that increased thymidine kinase-driven luciferase reporter activity in HepG2 cells more than 5-fold, regardless of orientation. Electrophoretic mobility shift assays (EMSAs) identified sequencespecific nuclear protein binding to the 59-bp repeats that was dependent on a 17-bp sequence containing a canonical GATA binding site (WGATAR). Competitive and supershift EMSA identified the participation of GATA4, another GATA family member or GATA-like factor, and a third factor unrelated to the GATA family. Involvement of the tricho-rhino-phalangeal syndrome-1 factor, which also binds a GATA sequence, was eliminated. Rather, competitive EMSA using known binding sequences for the orphan nuclear receptors, steroidogenic factor-1 (or NR5A1), and fetoprotein transcription factor (or NR5A2) implicated an NR5A member in binding a sequence overlapping the canonical GATA. Chromatin immunoprecipitation assay demonstrated in vivo binding of NR5A2 to the enhancer sequence in human hepatocytes. The enhancer sequence is conserved within the human population but seems species-specific. The identification of this novel enhancer and its putative mechanism adds to the complexities of human CYP2E1 regulation.CYP2E1 is highly expressed in liver, in which it metabolizes a large number of small molecular weight endogenous or exogenous compounds (Lieber, 1999). CYP2E1 converts some chemicals to a more toxic form; for example, it is the major enzyme responsible for the oxidation of acetaminophen to the reactive quinone, NAPQI. The more than 20-fold interindividual variation in human CYP2E1 activity has been attributed to diverse regulatory mechanisms acting at both transcriptional and post-transcriptional levels (Lieber, 1999). CYP2E1 genetic variants have been found within the structural gene and upstream sequences; however, the majority have not demonstrated an in vivo functional impact (Carrière et al., 1996). An exception is a polymorphism in the CYP2E1 promoter CYP2E1*1D, which has been associated with increased in vivo metabolic activity with ethanol intake and obesity (McCarver et al., 1998). In part because of the emphasis on post-transcriptional regulation, knowledge regarding mechanisms responsible for the control of CYP2E1 transcription has lagged. We report here the use of adenovirus representing the CYP2E1*1D allele and the reference sequence CYP2E1*1C to identify a novel enhancer in the far CYP2E1 upstream region (CYP2E1*1C position Ϫ3690 to Ϫ...

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Mutations ofZFPM2/FOG2 gene in sporadic cases of tetralogy of Fallot

Cited by 123 publications

References 22 publications

Epidemiology and Etiology of Congenital Heart Diseases

Epidemiology and Etiology of Congenital Heart Diseases

Multiplex Ligation-Dependent Probe Amplification Analysis ofGATA4Gene Copy Number Variations in Patients with Isolated Congenital Heart Disease

Identification and Functional Analysis of a Novel HumanCYP2E1Far Upstream Enhancer

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