Ebstein anomaly

Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Ebstein anomaly is an uncommon congenital heart defect (CHD), characterized by downward displacement of the tricuspid valve into the right ventricle. To uncover the genetic associations with Ebstein anomaly, we have searched chromosomal imbalances using standard cytogenetic and array-CGH analysis, and single gene conditions associated with syndromic Ebstein anomaly (with extracardiac anomalies), and screened GATA4 and NKX2.5 mutations in nonsyndromic patients (without extracardiac anomalies). Between January 1997 and September 2009, 44 consecutive patients with Ebstein anomaly were evaluated in two centers of Pediatric Cardiology. Ebstein anomaly was syndromic in 12 (27%) patients, and nonsyndromic in 32 (73%). A recognizable syndrome or complex was diagnosed by clinical criteria in seven patients. In one syndromic patient an 18q deletion was diagnosed by standard cytogenetic analysis. Array-CGH analysis performed in 10 of the 12 syndromic patients detected an interstitial deletion of about 4Mb at 8p23.1 in one patient, and a deletion 1pter>1p36.32/dup Xpter->Xp22.32 in another patient. In the 28 of 32 nonsyndromic patients who underwent molecular testing, no mutation in GATA4 and NKX2.5 genes were detected. We conclude that Ebstein anomaly is a genetically heterogeneous defect, and that deletion 1p36 and deletion 8p23.1 are the most frequent chromosomal imbalances associated with Ebstein anomaly. Candidate genes include the GATA4 gene (in patients with del 8p23.1), NKX2.5 (based on published patients with isolated Ebstein anomaly) and a hypothetical gene in patients with del 1p36).

Original languageEnglish
Pages (from-to)2196-2202
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume155
Issue number9
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Ebstein Anomaly
Genetic Heterogeneity
Genes
Mutation
Tricuspid Valve
Congenital Heart Defects
Cytogenetic Analysis
Cardiology
Cytogenetics
Heart Ventricles

Keywords

  • CGHarray
  • Deletion 8p23
  • Ebstein anomaly
  • Microdeletion 1p36

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

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title = "Ebstein anomaly: Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1",
abstract = "Ebstein anomaly is an uncommon congenital heart defect (CHD), characterized by downward displacement of the tricuspid valve into the right ventricle. To uncover the genetic associations with Ebstein anomaly, we have searched chromosomal imbalances using standard cytogenetic and array-CGH analysis, and single gene conditions associated with syndromic Ebstein anomaly (with extracardiac anomalies), and screened GATA4 and NKX2.5 mutations in nonsyndromic patients (without extracardiac anomalies). Between January 1997 and September 2009, 44 consecutive patients with Ebstein anomaly were evaluated in two centers of Pediatric Cardiology. Ebstein anomaly was syndromic in 12 (27{\%}) patients, and nonsyndromic in 32 (73{\%}). A recognizable syndrome or complex was diagnosed by clinical criteria in seven patients. In one syndromic patient an 18q deletion was diagnosed by standard cytogenetic analysis. Array-CGH analysis performed in 10 of the 12 syndromic patients detected an interstitial deletion of about 4Mb at 8p23.1 in one patient, and a deletion 1pter>1p36.32/dup Xpter->Xp22.32 in another patient. In the 28 of 32 nonsyndromic patients who underwent molecular testing, no mutation in GATA4 and NKX2.5 genes were detected. We conclude that Ebstein anomaly is a genetically heterogeneous defect, and that deletion 1p36 and deletion 8p23.1 are the most frequent chromosomal imbalances associated with Ebstein anomaly. Candidate genes include the GATA4 gene (in patients with del 8p23.1), NKX2.5 (based on published patients with isolated Ebstein anomaly) and a hypothetical gene in patients with del 1p36).",
keywords = "CGHarray, Deletion 8p23, Ebstein anomaly, Microdeletion 1p36",
author = "Digilio, {Maria Cristina} and Laura Bernardini and Francesca Lepri and Giuffrida, {Maria Grazia} and Valentina Guida and Anwar Baban and Paolo Versacci and Rossella Capolino and Barbara Torres and {De Luca}, Alessandro and Antonio Novelli and Bruno Marino and Bruno Dallapiccola",
year = "2011",
month = "9",
doi = "10.1002/ajmg.a.34131",
language = "English",
volume = "155",
pages = "2196--2202",
journal = "American Journal of Medical Genetics, Part A",
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TY - JOUR

T1 - Ebstein anomaly

T2 - Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1

AU - Digilio, Maria Cristina

AU - Bernardini, Laura

AU - Lepri, Francesca

AU - Giuffrida, Maria Grazia

AU - Guida, Valentina

AU - Baban, Anwar

AU - Versacci, Paolo

AU - Capolino, Rossella

AU - Torres, Barbara

AU - De Luca, Alessandro

AU - Novelli, Antonio

AU - Marino, Bruno

AU - Dallapiccola, Bruno

PY - 2011/9

Y1 - 2011/9

N2 - Ebstein anomaly is an uncommon congenital heart defect (CHD), characterized by downward displacement of the tricuspid valve into the right ventricle. To uncover the genetic associations with Ebstein anomaly, we have searched chromosomal imbalances using standard cytogenetic and array-CGH analysis, and single gene conditions associated with syndromic Ebstein anomaly (with extracardiac anomalies), and screened GATA4 and NKX2.5 mutations in nonsyndromic patients (without extracardiac anomalies). Between January 1997 and September 2009, 44 consecutive patients with Ebstein anomaly were evaluated in two centers of Pediatric Cardiology. Ebstein anomaly was syndromic in 12 (27%) patients, and nonsyndromic in 32 (73%). A recognizable syndrome or complex was diagnosed by clinical criteria in seven patients. In one syndromic patient an 18q deletion was diagnosed by standard cytogenetic analysis. Array-CGH analysis performed in 10 of the 12 syndromic patients detected an interstitial deletion of about 4Mb at 8p23.1 in one patient, and a deletion 1pter>1p36.32/dup Xpter->Xp22.32 in another patient. In the 28 of 32 nonsyndromic patients who underwent molecular testing, no mutation in GATA4 and NKX2.5 genes were detected. We conclude that Ebstein anomaly is a genetically heterogeneous defect, and that deletion 1p36 and deletion 8p23.1 are the most frequent chromosomal imbalances associated with Ebstein anomaly. Candidate genes include the GATA4 gene (in patients with del 8p23.1), NKX2.5 (based on published patients with isolated Ebstein anomaly) and a hypothetical gene in patients with del 1p36).

AB - Ebstein anomaly is an uncommon congenital heart defect (CHD), characterized by downward displacement of the tricuspid valve into the right ventricle. To uncover the genetic associations with Ebstein anomaly, we have searched chromosomal imbalances using standard cytogenetic and array-CGH analysis, and single gene conditions associated with syndromic Ebstein anomaly (with extracardiac anomalies), and screened GATA4 and NKX2.5 mutations in nonsyndromic patients (without extracardiac anomalies). Between January 1997 and September 2009, 44 consecutive patients with Ebstein anomaly were evaluated in two centers of Pediatric Cardiology. Ebstein anomaly was syndromic in 12 (27%) patients, and nonsyndromic in 32 (73%). A recognizable syndrome or complex was diagnosed by clinical criteria in seven patients. In one syndromic patient an 18q deletion was diagnosed by standard cytogenetic analysis. Array-CGH analysis performed in 10 of the 12 syndromic patients detected an interstitial deletion of about 4Mb at 8p23.1 in one patient, and a deletion 1pter>1p36.32/dup Xpter->Xp22.32 in another patient. In the 28 of 32 nonsyndromic patients who underwent molecular testing, no mutation in GATA4 and NKX2.5 genes were detected. We conclude that Ebstein anomaly is a genetically heterogeneous defect, and that deletion 1p36 and deletion 8p23.1 are the most frequent chromosomal imbalances associated with Ebstein anomaly. Candidate genes include the GATA4 gene (in patients with del 8p23.1), NKX2.5 (based on published patients with isolated Ebstein anomaly) and a hypothetical gene in patients with del 1p36).

KW - CGHarray

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KW - Ebstein anomaly

KW - Microdeletion 1p36

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DO - 10.1002/ajmg.a.34131

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JF - American Journal of Medical Genetics, Part A

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