Next-Generation Sequencing Identifies Different Genetic Defects in 2 Patients with Primary Adrenal Insufficiency and Gonadotropin-Independent Precocious Puberty

Chiara Guzzetti, Carla Bizzarri, Elisa Pisaneschi, Mafalda Mucciolo, Emanuele Bellacchio, Anastasia Ibba, Letizia Casula, Antonio Novelli, Sandro Loche, Marco Cappa

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The development of gonadotropin-independent (peripheral) precocious puberty in male children with primary adrenal insufficiency (PAI) is consistent with a defect in the genes encoding for the enzymes involved in steroid hormone biosynthesis.

METHODS: Two young boys presented with peripheral precocious puberty followed by PAI. In both patients, the analysis of CYP21A2 gene encoding 21-hydroxylase was normal. As a second step, a targeted next-generation sequencing (NGS) was performed in both patients using a customized panel of congenital endocrine disor ders.

RESULTS: Case 1 had a new homozygous variant in the CYP11B1 gene (c.1121+5G>A). Mutations of this gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency, an essential enzyme in the cortisol biosynthesis pathway. Case 2 showed a new hemizygous mutation in the NR0B1 gene (c.1091T>G), which encodes for DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita [AHC] and critical region on the X chromosome gene 1). NR0B1 mutations cause X-linked AHC and hypogonadotropic hypogonadism. Pathogenicity prediction software defined both mutations as probably damaging.

CONCLUSIONS: Peripheral precocious puberty was the atypical presentation of 2 rare genetic diseases. The use of NGS made the characterization of these 2 cases with similar clinical phenotypes caused by 2 different genetic defects possible.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalHormone Research in Paediatrics
DOIs
Publication statusE-pub ahead of print - Sep 4 2018

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