title: De novo 9q gain in an infant with tetralogy of Fallot with absent pulmonary valve: Patient report and review of congenital heart disease in 9q duplication syndrome.
abstract: Genomic disruptions, altered epigenetic mechanisms, and environmental factors contribute to the heterogeneity of congenital heart defects (CHD). In recent years, chromosomal microarray analysis (CMA) has led to the identification of numerous copy number variations (CNV) in patients with CHD. Genes disrupted by and within these CNVs thus represent excellent candidate genes for CHD. Microduplications of 9q (9q+) have been described in patients with CHD, however, the critical gene locus remains undetermined. Here we discuss an infant with tetralogy of Fallot with absent pulmonary valve, fetal hydrops, and a 3.76 Mb de novo contiguous gain of 9q34.2-q34.3 detected by CMA, and confirmed by karyotype and FISH studies. This duplicated interval disrupted RXRA (retinoid X receptor alpha; OMIM #180245) at intron 1. We also review CHD findings among previously reported patients with 9q (9q+) duplication syndrome. This is the first report implicating RXRA in CHD with 9q duplication, providing additional data in understanding the genetic etiology of tetralogy of Fallot, CHD, and disorders linked to 9q microduplication syndrome. This report also highlights the significance of CMA in the clinical diagnosis and genetic counseling of patients and families with complex CHD.
authors.affiliation: Department of Pathology and Immunology, Cytogenomics Laboratory, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Ina E
authors.initials: IE
authors.lastname: Amarillo
authors.affiliation: Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Shawn
authors.initials: S
authors.lastname: O'Connor
authors.affiliation: Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Marcia
authors.initials: M
authors.lastname: Willing
authors.affiliation: Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wambach
mesh_terms: D002899:Chromosomes, Human, Pair 9; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D011664:Pulmonary Valve / Q000002:abnormalities*; D047490:Retinoid X Receptor alpha / Q000235:genetics; D013771:Tetralogy of Fallot / Q000209:etiology / Q000235:genetics*; D014314:Trisomy
chemical_list: D047490:Retinoid X Receptor alpha
keywords: RXRA; retinoid X receptor alpha; tetralogy of Fallot with absent pulmonary valve