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 4 Mb 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).
authors.affiliation: Medical Genetics and Pediatric Cardiology, Bambino Gesù Pediatric Hospital, IRCCS, Rome, Italy. digilio@opbg.net
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Francesca
authors.initials: F
authors.lastname: Lepri
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Giuffrida
authors.forename: Valentina
authors.initials: V
authors.lastname: Guida
authors.forename: Anwar
authors.initials: A
authors.lastname: Baban
authors.forename: Paolo
authors.initials: P
authors.lastname: Versacci
authors.forename: Rossella
authors.initials: R
authors.lastname: Capolino
authors.forename: Barbara
authors.initials: B
authors.lastname: Torres
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004437:Ebstein Anomaly / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D008297:Male