[Identification of a novel missense mutation of the DAX-1 gene in a Chinese pedigree with X-linked adrenal hypoplasia congenita].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Xiao
Yuan
Y
Department of Pediatrics, Laboratory of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Yang
Jun
J
Zhang
Hui-jie
HJ
Wang
Wei
W
Li
Xiao-ying
XY
Wang
De-fen
DF
Dong
Zhi-ya
ZY
Wang
Xiu-min
XM
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002648:Child; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
D057137:DAX-1 Orphan Nuclear Receptor; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins