Loke Kah-Yin, Poh Larry Kok-Seng, Lee Warren Wei-Rhen, Lai Poh-San
Department of Paediatrics, National University Hospital of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
Horm Res. 2009;71(5):298-304. doi: 10.1159/000208804. Epub 2009 Apr 1.
BACKGROUND/AIMS: X-linked adrenal hypoplasia congenita (AHC) is typically associated with DAX-1 mutations and hypogonadotropic hypogonadism. However, atypical cases of X-linked AHC in association with central precocious puberty and even normal puberty have rarely been reported, although the mechanism of action remains unknown.
This is a case report of a boy with X-linked AHC associated with Duchenne muscular dystrophy, whose clinical presentation led to analysis of the DAX-1, glycerol kinase (GK1) and dystrophin genes, which were amplified by polymerase chain reaction, with Southern blot analysis of the AHC locus.
There was a non-contiguous deletion of the DAX-1 and GK1 genes, with deletion of the dystrophingene from exons 3 to 79.
This is the first report of X-linked AHC, central precocious puberty in the absence of the DAX-1 gene. The fact that a 'loss of function' DAX-1 mutation can be associated with hypogonadotropic hypogonadism, precocious and normal puberty, suggests that DAX-1 is but one of several transcription factors which regulate puberty, and provides further evidence that other transcription factors may interact with DAX-1 and influence gonadal regulation in a complex, but hierarchical fashion.
背景/目的：X连锁先天性肾上腺发育不全（AHC）通常与DAX-1突变及低促性腺激素性性腺功能减退相关。然而，X连锁AHC合并中枢性性早熟甚至正常青春期的非典型病例鲜有报道，其作用机制尚不清楚。
本文报告1例患有X连锁AHC并合并杜氏肌营养不良的男孩，其临床表现促使对DAX-1、甘油激酶（GK1）和肌营养不良蛋白基因进行分析，这些基因通过聚合酶链反应扩增，并对AHC基因座进行Southern印迹分析。
DAX-1和GK1基因存在非连续性缺失，肌营养不良蛋白基因外显子3至79缺失。
本文首次报道了X连锁AHC、在无DAX-1基因情况下的中枢性性早熟。“功能丧失”的DAX-1突变可与低促性腺激素性性腺功能减退、性早熟及正常青春期相关，这一事实表明DAX-1只是调节青春期的几种转录因子之一，并进一步证明其他转录因子可能与DAX-1相互作用，以复杂但分级的方式影响性腺调节。
