A new DAX1 gene mutation associated with congenital adrenal hypoplasia and hypogonadotropic hypogonadism
A new DAX1 gene mutation associated with congenital adrenal hypoplasia and hypogonadotropic hypogonadism
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DOI：
10.1002/ajmg.a.30689
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发表时间：
2005-06-15
影响因子：
2
通讯作者：
Cicognani, A
中科院分区：
文献类型：
--
作者：
Balsamo, A;Antelli, A;Cicognani, A
我们报告的DAX1基因调查的患者与X连锁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症（HH），以确定突变导致这种疾病，并确认临床诊断。还报告了详细记录纵向数据的条件的临床过程的描述。一名男性新生儿在出生45天时因呕吐、脱水和体重减轻而被转诊。诊断为原发性肾上腺功能不全。由于一方面ACTH水平升高，另一方面骨龄进行性延迟，在青春期前使用糖皮质激素治疗的适当性难以判断。在整个检查期间，基础和GnRH刺激的促性腺激素水平保持较低，开始外源性促性腺激素治疗。在14.6岁时，由于左后顶叶区域发生了3度间变性室管膜瘤，没有明显的软脑膜受累，因此不得不中断。先证者DAX1基因第2外显子AAT缺失，导致Asn430缺失。在母亲和祖母身上没有发现任何变化。该缺失的残基位于形成配体结合结构域（LBD）疏水核心的螺旋之一中;因此该突变可能是观察到的表型的原因。需要进一步研究以证实其在HH相关AHC中的因果作用。(c)2005 Wiley-Liss，Inc.
We report on a DAX1 gene investigation in a patient with X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) in order to identify mutations causing this disorder and to confirm the clinical diagnosis. The description of the clinical course of the condition with a detailed documentation of longitudinal data is also reported. A male newborn was referred at 45 days of life because of vomiting, dehydration, and weight loss. The diagnosis was primary adrenal insufficiency. The appropriateness of glucocorticoid therapy during the prepubertal period was difficult to judge because of elevated ACTH levels on one hand and progressive retardation of bone age on the other hand. Basal and GnRH stimulated gonadotropin levels remained low during the entire period of examination and exogenous gonadotropin treatment was begun. This had to be interrupted at age 14.6 years because of the occurrence of a 3rd degree anaplastic ependimoma of the left posterior-parietal region, without apparent leptomeningeal involvement. The molecular analysis of DAX1 gene of the propositus showed deletion of nucleotides AAT in exon 2, resulting in the loss of the Asn430. No alterations were found in the mother and grandmother. This deleted residue lies in one of the helices forming the hydrophobic core of the ligand-binding domain (LBD); thus this mutation may be the cause of the observed phenotype. Further investigations are needed to verify its causal role in AHC associated with HH. (c) 2005 Wiley-Liss, Inc.