title: A novel DAX1/NR0B1 mutation in a patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism.
abstract: 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.
authors.affiliation: Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Claudilene
authors.initials: C
authors.lastname: Battistin
authors.forename: Hamilton Cabral de
authors.initials: HC
authors.lastname: Menezes Filho
authors.forename: Sorahia
authors.initials: S
authors.lastname: Domenice
authors.forename: Mirian Yumie
authors.initials: MY
authors.lastname: Nishi
authors.forename: Thais
authors.initials: T
authors.lastname: Della Manna
authors.forename: Hilton
authors.initials: H
authors.lastname: Kuperman
authors.forename: Leandra
authors.initials: L
authors.lastname: Steinmetz
authors.forename: Vaê
authors.initials: V
authors.lastname: Dichtchekenian
authors.forename: Nuvarte
authors.initials: N
authors.lastname: Setian
authors.forename: Durval
authors.initials: D
authors.lastname: Damiani
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000309:Adrenal Insufficiency; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D000075262:Hypoadrenocorticism, Familial; D007006:Hypogonadism / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor