Table I.

GATA4 Alterations in Familial Heart Defects

Reference	Alteration (AA change)	Phenotype	Penetrance	Families	Control chromosomes	Functional studies
Garg et al., 2003	Gly296Ser	Non-syndromic ASD (+/- VSD, PVS, cardiac valve insufficiency, AVSD)	100% of clinically evaluated affected individuals	1 Family	0/6000 (and 0/10 evaluated unaffected family members)	Disrupted interaction with TBX5, decreased DNA binding affinity, hypomorphic transactivation ability
	Glu359fs	Non-syndromic ASD	100% of evaluated affected individuals	1 family	0/6000 (and 0/2 evaluated unaffected family members)	Transcriptionally inactive
Okubo et al., 2004	Ser358fs	ASD +/- PS	100% of clinically evaluated affected individuals	1 family	0/200 (and 0/13 evaluated unaffected family members)	Frameshift & premature STOP codon at amino acid 403, likely results in haploinsufficiency, similar to 1075delG described by Garg et al., 2003
Sarkozy et al., 2005b	Gly296Ser	ASD, PVS, no conduction abnormalities	2/2 Affected individuals (family 1), 3/3 clinically evaluated affected individuals (family 2)	2/16 Families total	NR	See Garg et al., 2003
Hirayama-Yamada et al., 2005	Glu359fs	ASD (5 individuals) dextrocardia (1 individual)	6/7 Affected individuals (family 1)	1 Family/16 families	NR
	Ser52Phe	ASD (3 individuals)	3/3 Affected individuals (family 2)	1 Family/16 families	0/202 Control chromosomes from healthy Japanese individuals	Decreased transcriptional activity (Schluterman et al., 2007), normal subcellular localization & DNA binding activity, Ser52 located in transactivation domain 1 (TAD1)

ASD, atrial septal defect; AVSD, atrioventricular septal defect; NR, not reported; PS, pulmonary stenosis; PVS, pulmonary valve stenosis; VSD, ventricular septal defect.