title: Prenatal diagnosis of two fetuses with deletions of 8p23.1, critical region for congenital diaphragmatic hernia and heart defects.
abstract: Microdeletions of 8p23.1 are mediated by low copy repeats and can cause congenital diaphragmatic hernia (CDH) and cardiac defects. Within this region, point mutations of the GATA4 gene have been shown to cause cardiac defects. However, the cause of CDH in these deletions has been difficult to determine due to the paucity of mutations that result in CDH, the lack of smaller deletions to refine the region and the reduced penetrance of CDH in these large deletions. Mice deficient for one copy of the Gata4 gene have been described with CDH and heart defects suggesting mutations in Gata4 can cause the phenotype in mice. We report on the SNP microarray analysis on two fetuses with deletions of 8p23.1. The first had CDH and a ventricular septal defect (VSD) on ultrasonography and a family history of a maternal VSD. Microarray analysis detected a 127-kb deletion which included the GATA4 and NEIL2 genes which was inherited from the mother. The second fetus had an incomplete atrioventricular canal defect on ultrasonography. Microarray analysis showed a 315-kb deletion that included seven genes, GATA4, NEIL2, FDFT1, CTSB, DEFB136, DEFB135, and DEFB134. These results suggest that haploinsufficiency of the two genes in common within 8p23.1; GATA4 and NEIL2 can cause CDH and cardiac defects in humans.
authors.affiliation: Department of Cytogenetics, Laboratory Corporation of America/Dynacare, Seattle, WA 98122, USA. keitgee@labcorp.com
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Keitges
authors.forename: Romela
authors.initials: R
authors.lastname: Pasion
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Burnside
authors.forename: Carla
authors.initials: C
authors.lastname: Mason
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez-Ruiz
authors.forename: Teresa
authors.initials: T
authors.lastname: Dunn
authors.forename: Meredith
authors.initials: M
authors.lastname: Masiello
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gebbia
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Fernandez
authors.forename: Hiba
authors.initials: H
authors.lastname: Risheg
mesh_terms: D002898:Chromosomes, Human, Pair 8; D045647:DNA Glycosylases / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics; D057895:Haploinsufficiency; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D006345:Heart Septal Defects, Ventricular / Q000000981:diagnostic imaging / Q000235:genetics; D006548:Hernia, Diaphragmatic / Q000000981:diagnostic imaging / Q000235:genetics*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D007231:Infant, Newborn; D009006:Monosomy; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis; D016216:Ultrasonography, Prenatal
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C473642:NEIL2 protein, human