Ebstein anomaly: Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1

Digilio, María Cristina; Bernardini, Laura; Lepri, Francesca; Giuffrida, Maria Grazia; Guida, Valentina; Baban, Anwar; Versacci, Paolo; Capolino, Rossella; Torres, Bárbara; Luca, Alessandro De; Novelli, Antonio; Marino, Bruno; Dallapiccola, Bruno

doi:10.1002/ajmg.a.34131

Cited by 44 publications

(32 citation statements)

References 37 publications

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“…Familial incidence of the defect was observed, what was confirmed in studies on familial incidence of some gene mutations (12). Certain genetic researches indicated that EA is geneti-cally heterogeneous defect which could be associated with some chromosomal microdeletions (13).…”

Section: Introductionsupporting

confidence: 52%

Ebstein Anomaly

Pajak

2013

Journal of Rare Cardiovascular Diseases

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Ebstein anomaly (EA) is a rare congenital malformation of the heart that is characterized by apical displacement of the septal and posterior tricuspid valve leaflets, with atrialization of the right ventricle and variable degree of malformation and displacement of the anterior leaflet. Patients can have a variety of symptoms related to the anatomic abnormalities of EA and their hemodynamic effects or associated structural and conduction system disease. Most frequently cyanosis, palpitations, fatigue and dyspnea can be observed. In severe forms edema and ascites. Treatment of EA is complex and depends of the severity of the disease itself and the effect of accompanying congenital structural and electrical abnormalities. Options of treatment include medical therapy, radiofrequency ablation, and surgical therapy. Main aim of the surgical therapy is to correct the underlying tricuspid valve, right ventricular abnormalities and any associated intracardiac defects if exist. Palliative procedures and cardiac transplantation can be considered in most sever EA patients. JRCD 2013; 1 (4): 139-143

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Section: Introductionsupporting

confidence: 52%

Ebstein Anomaly

Pajak

2013

Journal of Rare Cardiovascular Diseases

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“…On the other hand, there are many reports which show an association between Ebstein anomaly and 1p36 deletion [7,[37][38][39][40]. The genomic region responsible for Ebstein anomaly was assigned to the 2.9-3.8 Mb region [39,40].…”

Section: Cardiac Abnormalitymentioning

confidence: 99%

Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications

Shimada¹,

Shimojima²,

Okamoto³

et al. 2015

Brain and Development

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“…Of note, 1p36 deletions have occasionally been associated with this rare malformation, and this case adds further evidence of a link between this rare heart abnormality and haploinsufficiency of one or more genes at 1p36. 17,18 In the fetus KUL 4, referred due to semi-lobar holoprosencephaly, a novel 2-Mb de novo deletion of 10q24.31-q24.32 was observed. Within the deleted region, several genes are located.…”

Section: Submicroscopic Cnvsmentioning

confidence: 99%

A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors

Brady

Chiaie

Christenhusz

et al. 2014

Genetics in Medicine

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Original research article INTRODUCTIONConventional karyotyping has been considered the gold standard for routine prenatal genetic diagnosis for many decades now, allowing for microscopic visualization and inspection of chromosomes and thus detection of numerical and structural chromosomal rearrangements. The main limitations are the resolution achieved by G-banding, which is limited to 5-10 Mb at best, and the requirement for cultured cells, needing a minimum of 8-10 days. The introduction of targeted methods of analysis such as fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) overcome the time constraints and resolution limitations inherent to karyotyping but do not provide a genome-wide analysis.1 More recently, molecular karyotyping using genomic microarrays has reached mainstream use in the postnatal diagnostic setting, providing a genome-wide screen for genomic imbalances at a far superior resolution to karyotyping.2 A number of studies have demonstrated the feasibility of prenatal diagnosis by genomic arrays using a variety of platforms, 3-7 but challenges remain in applying high-resolution genomic arrays to prenatal diagnosis. 6,8,9 One of the major ethical issues often raised is how to deal with variants of uncertain significance (VOUS) or risk loci, the detection of which leads to additional challenges for genetic counseling of parents. Furthermore, array analysis may reveal an imbalance for known "risk loci" where the future penetrance is uncertain or may be associated with variable expression. The penetrance risks for a number of recurrent copy-number variations (CNVs) have been estimated based on the frequencies in patients and controls. [10][11][12] However, although it is possible to calculate a populationbased risk, it is impossible in the prenatal setting to predict the phenotypic outcome in the child. Purpose:To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound. Methods: Patients referred for prenatal diagnosis due to ultrasound anomalies underwent analysis by array comparative genomic hybridization as the first-tier diagnostic test.Results: A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization. Array analysis revealed causal imbalances in a total of 9.6% of patients (n = 37). Submicroscopic copy-number variations were detected in 2.6% of patients (n = 10/37), and arrays added valuable information over conventional karyotyping in 3.9% of patients (n = 15/37). We highlight a novel advantage of arrays; a 500-kb paternal insertional translocation is the likely driver of a de novo unbalanced translocation, thus improving recurrence risk calculation in this family. Variants of uncertain significance were revealed in 1.6% of patients (n = 6/383). Conclusion:We demonstrate the added value of chromosomal microarrays for prenatal diagnosis in the presence of ultrasound anomalies. We advocate reporting back on...

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Ebstein anomaly: Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1

Cited by 44 publications

References 37 publications

Ebstein Anomaly

Ebstein Anomaly

Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications

A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors

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