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Horm Res Paediatr. 2018;90(3):203-211. doi: 10.1159/000492496. Epub 2018 Sep 4.

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

Author information

1
Pediatric Endocrine Unit, Pediatric Hospital Microcitemico "Antonio Cao," AO Brotzu, Cagliari, Italy.
2
Endocrinology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italycarla.bizzarri@opbg.net.
3
Medical Genetics Laboratory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
4
Genetic and Rare Diseases, Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
5
Endocrinology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

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.

KEYWORDS:

11β-Hydroxylase; Adrenal insufficiency; CYP11B1; DAX1; NR0B1; Precocious puberty

PMID:
30179867
DOI:
10.1159/000492496
[Indexed for MEDLINE]

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