Novel missense mutation (Leu466Arg) of the DAX1 gene in a patient with X-linked congenital adrenal hypoplasia

We identified a DAX1 missense mutation, a substitution of arginine for leuc ine at codon 466 (Leu466Arg), in an infant with X-linked congenital adrenal hypoplasia (AHC), A heterozygous substitution, Leu466Arg, was also identif ied in his mother and sister. Since leucine at position 466 is well conserv ed among other orphan nuclear hormone receptor superfamilies and Leu466Arg was not detected among 50 normal Japanese control individuals, the mutation is most likely responsible for X-linked AHC, Pt is interesting to note tha t Leu466Arg among all mutations ever reported is located at the most C-term inal region of the DAX-1 protein. Most mutations identified previously were located in the C-terminal presumptive ligand binding domain. Hence, the C- terminal end of the DAX-1 protein may play an important role in the biologi cal function, such as in normal adrenal embryogenesis, Am. J, Med, Genet. 8 4:87-89, 1999, (C) 1999 Wiley-Liss, Inc.