Xiao Yuan, Yang Jun, Zhang Hui-jie, Wang Wei, Li Xiao-ying, Wang De-fen, Dong Zhi-ya, Wang Xiu-min
Department of Pediatrics, Laboratory of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Zhonghua Er Ke Za Zhi. 2007 Dec;45(12):937-41.
Inactivating mutations of DAX-1 give rise to the X-linked form of adrenal hypoplasia congenita (AHC). Affected individuals are at risk of early postnatal Addisonian crisis, but the variable phenotypic expression of DAX-1 insufficiency renders this diagnosis challenging. This study aimed to understand the clinical features and identify DAX-1 gene mutation of the affected individuals and their relatives in a Chinese adrenal hypoplasia congenita kindred.
The proband was diagnosed as adrenal insufficiency shortly after birth and his elder cousin was also diagnosed as having this disease at the age of about 8 years. Clinical data were obtained from 2 affected individuals when they were hospitalized into the department of pediatrics, Ruijin Hospital in 2006; 20 peripheral blood samples were obtained from the affected individuals and their relatives; exons in DAX-1 gene were amplified, and PCR product was purified and sequenced directly for analyzing mutation.
A novel hemizygous mutation (T785C) was found in DAX-1 gene in both patients. Some clinical features such as the age of onset were different although these 2 patients carried the same mutation. There were 5 carriers of this mutation in the patients' maternal pedigree.
The results suggested that adrenal hypoplasia congenita in this kindred was caused by a novel mutation (T785C) in DAX-1 gene, and the same mutation can give rise to the variable phenotype.
DAX-1基因的失活突变会导致X连锁型先天性肾上腺发育不全（AHC）。患病个体有出生后早期发生肾上腺皮质功能减退危象的风险，但DAX-1功能不足的可变表型表达使该诊断具有挑战性。本研究旨在了解一个中国先天性肾上腺发育不全家系中患病个体及其亲属的临床特征，并鉴定DAX-1基因突变。
先证者出生后不久被诊断为肾上腺功能不全，其年长的堂兄在约8岁时也被诊断患有此病。2006年，从瑞金医院儿科收治的2名患病个体获取临床资料；从患病个体及其亲属采集20份外周血样本；扩增DAX-1基因的外显子，对PCR产物进行纯化并直接测序以分析突变情况。
两名患者的DAX-1基因均发现一个新的半合子突变（T785C）。尽管这两名患者携带相同的突变，但一些临床特征如发病年龄有所不同。患者母系家系中有5名该突变的携带者。
结果表明，该家系的先天性肾上腺发育不全是由DAX-1基因的一个新突变（T785C）引起的，相同的突变可导致可变的表型。
