TY - JOUR
T1 - GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease
AU - Pehlivan, Tugce
AU - Pober, Barbara R.
AU - Brueckner, Martina
AU - Garrett, Stacey
AU - Slaugh, Rachel
AU - Van Rheeden, Richard
AU - Wilson, David B.
AU - Watson, Michael S.
AU - Hing, Anne V.
PY - 1999/3/19
Y1 - 1999/3/19
N2 - Previous studies have shown that patients with deletion of distal human chromosome arm 8p may have congenital heart disease and other physical anomalies. 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 from 48 individuals with congenital heart disease and normal karyotypes failed to detect any submicroscopic deletions at the GATA4 locus. We conclude that 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 factor genes (e.g., TBX5, NKX2-5) causes congenital heart disease, we postulate that GATA-4 deficiency may contribute to the phenotype of patients with monosomy of 8p23.1.
AB - Previous studies have shown that patients with deletion of distal human chromosome arm 8p may have congenital heart disease and other physical anomalies. 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 from 48 individuals with congenital heart disease and normal karyotypes failed to detect any submicroscopic deletions at the GATA4 locus. We conclude that 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 factor genes (e.g., TBX5, NKX2-5) causes congenital heart disease, we postulate that GATA-4 deficiency may contribute to the phenotype of patients with monosomy of 8p23.1.
KW - Chromosome 8p23.1
KW - Congenital heart disease
KW - Heart development
KW - Transcription factor GATA-4
UR - http://www.scopus.com/inward/record.url?scp=0033582940&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1096-8628(19990319)83:3<201::AID-AJMG11>3.0.CO;2-V
DO - 10.1002/(SICI)1096-8628(19990319)83:3<201::AID-AJMG11>3.0.CO;2-V
M3 - Article
C2 - 10096597
AN - SCOPUS:0033582940
SN - 0148-7299
VL - 83
SP - 201
EP - 206
JO - American journal of medical genetics
JF - American journal of medical genetics
IS - 3
ER -