10.6084/m9.figshare.7042556.v1 Guzzetti C. Guzzetti C. Bizzarri C. Bizzarri C. Pisaneschi E. Pisaneschi E. Mucciolo M. Mucciolo M. Bellacchio E. Bellacchio E. Ibba A. Ibba A. Casula L. Casula L. Novelli A. Novelli A. Loche S. Loche S. Cappa M. Cappa M. Supplementary Material for: Next-Generation Sequencing Identifies Different Genetic Defects in 2 Patients with Primary Adrenal Insufficiency and Gonadotropin-Independent Precocious Puberty Karger Publishers 2018 Precocious puberty Adrenal insufficiency CYP11B1 11β-Hydroxylase NR0B1 DAX1 2018-09-04 12:57:04 Dataset https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Next-Generation_Sequencing_Identifies_Different_Genetic_Defects_in_2_Patients_with_Primary_Adrenal_Insufficiency_and_Gonadotropin-Independent_Precocious_Puberty/7042556 <b><i>Background:</i></b> 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. <b><i>Methods:</i></b> Two young boys presented with peripheral precocious puberty followed by PAI. In both patients, the analysis of <i>CYP21A2</i> 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. <b><i>Results:</i></b> Case 1 had a new homozygous variant in the <i>CYP11B1</i> 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 <i>NR0B1</i> 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). <i>NR0B1</i> mutations cause X-linked AHC<i></i> and hypogonadotropic hypogonadism. Pathogenicity prediction software defined both mutations as probably damaging. <b><i>Conclusions:</i></b> 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.