Choi Jin-Ho, Shin Young-Lim, Kim Gu-Hwan, Kim Youngho, Park Sangwook, Park Jung-Young, Oh Changkyu, Yoo Han-Wook
Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Horm Res. 2005;63(4):200-5. doi: 10.1159/000085557. Epub 2005 Apr 28.
X-linked adrenal hypoplasia congenita (AHC) is a condition clinically featuring adrenal insufficiency and hypogonadotropic hypogonadism caused by mutations of DAX-1. This study was undertaken to characterize the molecular defects of DAX-1 in 3 unrelated Korean patients with AHC.
Patient 1 is a 6-year-old boy who presented with a salt-losing adrenal crisis in the neonatal period. Patient 2 is a 3-year-old boy who manifested aspiration pneumonia and adrenal insufficiency at the age of 1 month. Patient 3 is a 7-year-old boy who developed an adrenal crisis at the age of 3 days. In each of these patients, DAX-1 was analyzed by direct DNA sequencing after polymerase chain reaction amplification of the entire coding region.
Direct sequencing of DAX-1 revealed two novel mutations, 1156_1157delCT in patient 1 and another novel nonsense mutation W105X in patient 2. Patient 3 had complete deletion of DAX-1. In patient 3, serum transaminases and creatine kinase levels were elevated while the glycerol kinase activity of leukocytes was decreased. Markedly elevated glycerol excretion was detected by urine organic acid analysis. Patient 3 was diagnosed as Xp21 contiguous gene syndrome associated with deletions of the entire IL1RAPL, GK genes and the C-terminal region of DMD gene.
Two novel mutations of DAX-1 were detected in 2 unrelated patients with AHC, and complete deletion of DAX-1 in a patient with Xp21 contiguous gene syndrome who also presented with glycerol kinase deficiency, Duchenne muscular dystrophy, and AHC.
X连锁先天性肾上腺发育不全（AHC）是一种临床特征为肾上腺功能不全和促性腺激素缺乏性性腺功能减退的疾病，由DAX-1基因突变引起。本研究旨在对3例无血缘关系的韩国AHC患者的DAX-1分子缺陷进行特征分析。
患者1为一名6岁男孩，新生儿期出现失盐性肾上腺危象。患者2为一名3岁男孩，1个月大时出现吸入性肺炎和肾上腺功能不全。患者3为一名7岁男孩，3天时发生肾上腺危象。对每例患者，在聚合酶链反应扩增整个编码区后，通过直接DNA测序分析DAX-1。
DAX-1的直接测序揭示了两个新突变，患者1为1156_1157delCT，患者2为另一个新的无义突变W105X。患者3的DAX-1完全缺失。在患者3中，血清转氨酶和肌酸激酶水平升高，而白细胞的甘油激酶活性降低。尿有机酸分析检测到甘油排泄明显升高。患者3被诊断为与整个IL1RAPL、GK基因和DMD基因C末端区域缺失相关的Xp21连续基因综合征。
在2例无血缘关系的AHC患者中检测到DAX-1的两个新突变，在一名患有Xp21连续基因综合征且同时伴有甘油激酶缺乏、杜氏肌营养不良和AHC的患者中检测到DAX-1完全缺失。
