GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease

Previous studies have shown that patients with deletion of distal human chr omosome arm 8p may have congenital heart disease and other physical anomali es. The gene encoding GATA-4, a zinc finger transcription factor implicated in cardiac gene expression and development, localizes to chromosome region 8p23.,1, To examine whether GATA-4 deficiency is present in patients with monosomy of 8p23.1 with congenital heart disease, we performed fluorescence in situ hybridization (FISH) with a GATA4 probe on cells from a series of patients with interstitial deletion of 8p23.1. Four individuals with del(8) (p23.1) and congenital heart disease were found to be haploinsufficient at the GATA4 locus by FISH. The GATA4 gene was not deleted in a fifth patient with del(8)(p23.1) who lacked cardiac anomalies. FISH analysis on cells fro m 48 individuals with congenital heart disease and normal karyotypes failed to detect any submicroscopic deletions at the GATA4 locus. We conclude tha t haploinsufficiency at the GATA4 locus is often seen in patients with del( 8)(p23.1) and congenital heart disease, Based on these findings and recent studies showing that haploinsufficiency for other cardiac transcription fac tor genes (e.g., TBX5, NKX2-5) causes congenital heart disease, we postulat e that GATA-4 deficiency may contribute to the phenotype of patients with m onosomy of 8p23.1. (C) 1999 Wiley-Liss, Inc.