Identification of a Novel Mutation (p.G328W) in the NR5A1 Gene in a Boy with 46, XY DSD: Case Report of Clinical, Endocrine and Genetic Features

Ortolano R

doi:10.31031/gjem.2017.01.000503

Abstract

Global Journal of Endocrinological Metabolism Identification of a Novel Mutation (p.G328W) in the NR5A1 Gene in a Boy with 46, XY DSD: Case Report of Clinical, Endocrine and Genetic Features Ortolano R1*, Baldazzi L1, Menabò S2, Balsamo A3, Cassio A2, Antona V4, Cimador M4, Corsello G4 and Giuffrè M4 1Department of Woman, Child Health and Urologic Diseases, Pediatric Unit, S.Orsola-Malpighi University Hospital, Italy 2Department of Medical and Surgical Sciences, Pediatric Unit, University of Bologna, Italy 3Center for Rare Endocrinologic Conditions (CARENDO BO; Endo-ERN), S.Orsola-Malpighi University Hospital, Bologna 4Department of Sciences for Health Promotion and Mother and Child Care G. D’Alessandro, Italy *Corresponding author: Ortolano R, Department of Woman, Child Health and Urologic Diseases, Pediatric Unit, S.Orsola-Malpighi University Hospital, Via Massarenti 11, 40138 Bologna, Italy September 15, 2017; Published: October 16, 2017 DOI: 10.31031/GJEM.2017.01.000503 ISSN: 2637-8019Volume1 Issue1

Highlights

The gene NR5A1 encodes for the Steroidogenic factor1 (SF1), a key regulator of the adrenal/gonadal development and function
Evaluation of the adrenal function was normal and no symptoms or signs of adrenal insufficiency have emerged during follow-up. This is the first description of the p.G328W mutation (Sequence reference NC_000023.10) of the NR5A1 gene that causes the replacement of a highly conserved residue of the ligand-binding domain (LBD) and very likely affects the SF1 action
This finding contributes to choose sex assignment and underlines the importance to perform the analysis of the NR5A1 gene in 46, XY Differences of Sex Development (DSD) patients with a Partial Androgen Insensitivity Syndrome (PAIS)-like phenotype

Summary

Introduction

The gene NR5A1 (nuclear receptor subfamily 5 group A member 1, OMIM +184757) encodes for the Steroidogenic factor (SF1), a key regulator of the adrenal/gonadal development and function. Heterozygous mutations of NR5A1 gene are associated, in 46, XY DSD patients, with a wide phenotypic spectrum of the external genitalia, with or without adrenal failure. We report a 46, XY newborn carrying a novel heterozygous NR5A1 mutation that presents with ambiguous genitalia without adrenal failure. 46, XY DSD, in particular, consist of a wide range of phenotypes, from very low under virilization through various degrees of ambiguity, to complete female appearance. They are caused by partial or total gonadal dysgenesis, defects of androgen synthesis/action or other causes. In mice and humans it is expressed very early in the urogenital ridge and continues to be highly expressed in the developing adrenal, gonad, ventromedial hypothalamus, and pituitary

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