GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes

Martinez De Lapiscina I,Riedl S,Pandey Av,De Mingo C,Fernández-Cancio M,Audi L,Camats N,Sinclair A,Rodriguez A,Castaño L,Flück Ce

doi:10.1530/ey.15.6.14

Abstract

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes

Highlights

Disorders of sex development (DSD) are defined as congenital conditions, in which development of chromosomal, gonadal, or anatomical sex is atypical [1]. 46,XY DSD includes disorders in male gonad determination and differentiation, androgen biosynthesis or action, and anti-Müllerian hormone (AMH) synthesis or action [1]
Biochemical and hormonal studies at presentation and during follow-up revealed more or less normal values, only undetectable and low AMH was remarkable (Table 2). She was seen by a pediatric cardiologist for a heart murmur and found to have a complex congenital heart defects (CHD), which was not detected in prenatal screening (Table 1)
We characterized three human GATA4 sequence variations found in three individuals with a 46,XY DSD phenotype with and without CHD

Summary

Introduction

Disorders of sex development (DSD) are defined as congenital conditions, in which development of chromosomal, gonadal, or anatomical sex is atypical [1]. 46,XY DSD includes disorders in male gonad determination and differentiation, androgen biosynthesis or action, and anti-Müllerian hormone (AMH) synthesis or action [1]. Disorders of sex development (DSD) are defined as congenital conditions, in which development of chromosomal, gonadal, or anatomical sex is atypical [1]. 46,XY DSD includes disorders in male gonad determination and differentiation, androgen biosynthesis or action, and anti-Müllerian hormone (AMH) synthesis or action [1]. In the last two decades, numerous genes have been found to cause 46,XY DSD [2]. In about 40% of 46,XY DSD individuals, the underlying genetic cause still remains unsolved. The GATA family of transcription factors consists of six members, three expressed in hematopoietic stem cells (GATA1–3) and three in tissues derived from mesoderm and endoderm, including heart, gonad, lung, liver, and gut (GATA4–6). GATA factors regulate tissue-specific gene expression either alone or in cooperation with other factors [3, 4]. While the C-terminal zinc finger region is required for the DNA recognition and binding, and the N-terminal zinc finger region contributes to the stability, both zinc fingers are necessary for protein–protein interactions with other transcription factors [4, 7]

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Conclusion