p.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche

Mahdieh Soveizi; Nejat Mahdieh; Aria Setoodeh; Fatemeh Sayarifard; Farzaneh Abbasi; Himangshu S Bose; Bahareh Rabbani; Ali Rabbani

doi:10.1155/2020/4329791

p.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche

Int J Endocrinol. 2020 May 15:2020:4329791. doi: 10.1155/2020/4329791. eCollection 2020.

Authors

Mahdieh Soveizi¹, Nejat Mahdieh^{1

2

3}, Aria Setoodeh^{2

4}, Fatemeh Sayarifard^{2

4}, Farzaneh Abbasi^{2

4}, Himangshu S Bose⁵, Bahareh Rabbani^{1

2

3}, Ali Rabbani^{2

4}

Affiliations

¹ Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
² Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
³ Cardigenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
⁴ Children's Medical Center Hospital, Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USA.

Abstract

Premature pubarche (PP) is the appearance of sexual hair in children before puberty. The PP phenotype may attribute to nonclassic congenital adrenal hyperplasia (NC-CAH). In this study, we investigated the role of CYP21A2 gene variants in patients with PP in the Iranian population. Forty patients (13 males and 27 females), clinically diagnosed with PP, were analyzed for molecular testing of CYP21A2 gene variants. Direct sequencing was performed for the samples. Also, gene dosage analysis was performed for the cases. Fourteen patients (35%) had a mutation of p.Gln318X and p.Val281Leu, out of which 10% had regulatory variants. Approximately 10% of the patients were homozygous (NC-CAH). 78.5% (11/14) of patients had trimodular RCCX of which 5 patients had two copies of CYP21A1P pseudogene. The prevalence of p.Val281Leu was higher than p.Gln318X in PP patients. In conclusion, CYP21A2 variant detection has implications in the genetic diagnosis of PP phenotype. The genetic characterization of the CYP21A2 gene is important for characterizing the variable phenotype of carriers and genetic counseling of PP and NC-CAH patients.