Battistin Claudilene, Menezes Filho Hamilton Cabral de, Domenice Sorahia, Nishi Mirian Yumie, Della Manna Thais, Kuperman Hilton, Steinmetz Leandra, Dichtchekenian Vaê, Setian Nuvarte, Damiani Durval
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Arq Bras Endocrinol Metabol. 2012 Nov;56(8):496-500. doi: 10.1590/s0004-27302012000800006.
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.
我们报告了一例因新型DAX1突变导致的先天性肾上腺发育不全（AHC）和低促性腺激素性性腺功能减退（HH）病例。一名19个月大、有色素沉着和发育不良的男孩前来我院接受检查。该患者的三个兄弟因肾上腺衰竭死亡，一名母系表亲患有肾上腺功能不全。排除了肾上腺脑白质营养不良。MRI显示垂体和下丘脑正常。血浆激素评估显示促肾上腺皮质激素水平升高（高达2790 pg/mL），而雄烯二酮、硫酸脱氢表雄酮、11-脱氧皮质醇和皮质醇水平降低。14岁时，该患者仍处于青春期前，体重43.6 kg（标准差：-0.87），身高161 cm（标准差：-0.36），身体比例正常。在促性腺激素释放激素（GnRH）试验中，促黄体生成素（LH）和促卵泡生成素（FSH）的基础值和最大值分别为0.6/2.1和<1.0/<1.0 U/L。分子研究鉴定出一种新型突变，该突变由DAX1外显子1中密码子372（AAC；天冬酰胺）缺失组成。在对200个正常个体等位基因的研究中未发现此突变。预测位点分析表明，这种位于DAX1配体结合域的改变可能会损害DAX1蛋白。我们推测，新型（p.Asp372del）DAX1突变可能会导致DAX1功能破坏，并且可能与该患者AHC和HH的发生有关。
