<scp>GATA4</scp> Single‐Amino Acid Deletion in a Male Patient With Congenital Heart Defects, Differences of Sex Development, and Diaphragmatic Hernia

Monoallelic loss-of-function variants of GATA4 have been implicated in congenital heart defects, 46,XY differences of sex development, and congenital diaphragmatic hernia (CDH). However, there is no report of GATA4-variant positive patients who concomitantly exhibited these three features. Furthermore, the genotype-phenotype correlation of GATA4 abnormality remains unclear. Here, we report a 2-year-old boy who exhibited pulmonary valve stenosis, multiple atrial septal defects, hypospadias, bifid scrotum, bilateral inguinal hernia, and CDH. Endocrine evaluations of the patient were indicative of partial testicular dysgenesis. Exome sequencing identified a de novo 3-bp deletion in GATA4 that has not been reported previously. The variant eliminated one amino acid from the highly conserved five-threonine repeat in the second zinc finger domain (c.829_831del, p.T277del). The variant was assessed as deleterious by in silico analyses and was scored as "likely pathogenic" by the American College of Medical Genetics and Genomics guidelines. Our findings indicate that the five-threonine repeat in the second zinc finger domain contributes to GATA4 function. These results broaden the spectrum of GATA4 pathogenic variants and highlight the phenotypic diversity resulting from GATA4 abnormalities.