• PMID: 23295288
• Gene Name: DAX1
• Condition: Adrenal hypoplasia congenita, hypogonadotropichypogonadism
• Association: The study proposes that the novel (p.Asp372del) DAX1 mutation might be able to cause a disruption of DAX1 function, and is probably involved in the development of AHC and HH in this patient.
• Mutation: (p.Asp372del) DAX1
• Population size: 205
• Population details: 205 (4 adrenal failure, 200 controls)
• Sex: Male
• Infertility type: Male infertility, Female infertility
• Associated genes: DAX1, NR0B1
• Other associated phenotypes: Adrenal hypoplasia congenita, hypogonadotropichypogonadism

A novel DAX1/NR0B1 mutation in a patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism

Battistin C, Menezes Filho HC, Domenice S, Nishi MY, Della Manna T, Kuperman H, Steinmetz L, Dichtchekenian V, Setian N, Damiani D.

We report a case of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to a novel DAX1 mutation. A 19-month-old boy with hyperpigmentation and failure to thrive came to our service for investigation. Three brothers of the patient had died due to adrenal failure, and a maternal cousin had adrenal insufficiency. Adrenoleukodystrophy was excluded. MRI showed normal pituitary and hypothalamus. Plasma hormone evaluation revealed high ACTH (up to 2,790 pg/mL), and low levels of androstenedione, DHEA-S, 11-deoxycortisol, and cortisol. At 14 years of age the patient was still prepubescent, his weight was 43.6 kg (SDS: -0.87) and his height was 161 cm (SDS: -0.36), with normal body proportions. In the GnRH test, basal and maximum values of LH and FSH were respectively 0.6/2.1 and < 1.0/< 1.0 U/L. Molecular investigation identified a novel mutation that consists of a deletion of codon 372 (AAC; asparagine) in exon 1 of DAX1. This mutation was not found in a study of 200 alleles from normal individuals. Prediction site analysis indicated that this alteration, located in the DAX1 ligand-binding domain, may damage DAX1 protein. We hypothesize that the novel (p.Asp372del) DAX1 mutation might be able to cause a disruption of DAX1 function, and is probably involved in the development of AHC and HH in this patient. FAU - Battistin, Claudilene AU - Battistin C AD - Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil. FAU - Menezes Filho, Hamilton Cabral de AU - Menezes Filho HC FAU - Domenice, Sorahia AU - Domenice S FAU - Nishi, Mirian Yumie AU - Nishi MY FAU - Della Manna, Thais AU - Della Manna T FAU - Kuperman, Hilton AU - Kuperman H FAU - Steinmetz, Leandra AU - Steinmetz L FAU - Dichtchekenian, Vaê AU - Dichtchekenian V FAU - Setian, Nuvarte AU - Setian N