A Rare Case of Precocious Puberty in a Child with a Novel GATA-4 Gene Mutation: Implications for Disorders of Sex Development (DSD) and Review of the Literature

Tommaso Aversa; Giovanni Luppino; Domenico Corica; Giorgia Pepe; Mariella Valenzise; Roberto Coco; Alessandra Li Pomi; Malgorzata Wasniewska

doi:10.3390/genes14081631

A Rare Case of Precocious Puberty in a Child with a Novel GATA-4 Gene Mutation: Implications for Disorders of Sex Development (DSD) and Review of the Literature

Genes (Basel). 2023 Aug 16;14(8):1631. doi: 10.3390/genes14081631.

Authors

Tommaso Aversa^{1

2}, Giovanni Luppino^{1

2}, Domenico Corica^{1

2}, Giorgia Pepe^{1

2}, Mariella Valenzise^{1

2}, Roberto Coco^{1

2}, Alessandra Li Pomi^{1

2}, Malgorzata Wasniewska^{1

2}

Affiliations

¹ Department of Human Pathology of Adulthood and Childhood, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
² Pediatric Unit, AOU Policlinico G. Martino, Via Consolare Valeria 1, 98125 Messina, Italy.

Abstract

Background: Disorders/Differences of sex development (DSD) are often due to disruptions of the genetic programs that regulate gonad development. The GATA-4 gene, located on chromosome 8p23.1, encodes GATA-binding protein 4 (GATA-4), a transcription factor that is essential for cardiac and gonadal development and sexual differentiation.

Case description: A child with a history of micropenis and cryptorchidism. At 8 years of age, he came under our observation for an increase in sexual pubic hair (pubarche). The laboratory parameters and the GnRH test suggested a central precocious puberty (CPP). Treatment with GnRH analogs was started, and we decided to perform genetic tests for DSD. The NGS genetic investigation showed a novel and heterozygous variant in the GATA-4 gene.

Discussion: In the literature, 26 cases with 46,XY DSD due to the GATA4 gene were reported.

Conclusion: The novel variant in the GATA-4 gene of our patient was not previously associated with DSD. This is the first case of a DSD due to a GATA-4 mutation that develops precocious puberty. Precocious puberty could be associated with DSD and considered a prelude to hypogonadism in some cases.

Keywords: GATA-4 gene; cryptorchidism; disorder/differences of sex development; micropenis; precocious puberty.

Publication types

Review
Case Reports

MeSH terms

Child
Disorders of Sex Development* / genetics
Gonadotropin-Releasing Hormone
Humans
Male
Mutation
Puberty, Precocious* / genetics
Sexual Development / genetics

Substances

Gonadotropin-Releasing Hormone

Grants and funding

This research received no external funding.