一种DAX-1基因移码突变（428delG）引起的X-连锁先天性肾上腺发育不良

A novel mutation of 428delG in DAX-1 gene causing X-linked adrenal hypoplasia congenital

目的研究1个X-连锁先天性肾上腺发育不良家系的临床特征，检测患者及其家属中是否存在相关DAX-1基因的突变。方法收集1个临床诊断X-连锁先天性肾上腺发育不良的家系中2例患者及亲属的临床资料和外周血标本；提取基因组DNA，设计4对引物扩增DAX-1基因的2个外显子，PCR扩增DAX-1的全部外显子，扩增产物经纯化后进行直接测序。测序结果在核苷酸序列数据库进行比较分析。结果两例患者（表兄弟）DAX-1基因第1外显子处均存在428delG半合子移码突变。而患者的基因型与其临床表型并不一致。家系中有3例女性（他们的母亲及外祖母）为此突变的杂合子，正常人及家族中其他成员无该位点突变。结论在1个中国人先天性肾上腺发育不良家系中发现DAX-1新的移码突变428delG。各种基因型与表现型之间并无相关性。

Objective To investigate the clinical features and to identify the DAX-1 gene mutation in a Chinese kindred with X-linked adrenal hypoplasia congenital （AHC）. Methods Clinical data and peripheral blood samples were obtained from the affected individuals and their relatives. The genomic DNA was isolated from whole blood. Four pairs of primers were used to amplify the two exons of the DAX-1 gene, and PCR products were purified and sequenced directly. Sequencing results were compared to the human DAX-1 sequence in the public database. Results A novel hemizygous frameshift mutation （428delG） in exon 1 of the DAX-1 gene was found in both patients （the index case and his cousin）. Some clinical features such as the age of onset were different although these 2 patients carried the same mutation. Three females in the family, including the mothers of the 2 patients and their grandmother were carriers of this mutation. No such mutation was detected in other healthy persons in the family. Conclusion The result suggested that X-linked AHC in the kindred was caused by a novel mutation of 428delG in theDAX-1 gene, and the same mutation can give rise to variable phenotypes.