Ongoing efforts in our laboratory have identified nine novel NR0B1 mutations in X-linked AHC patients (Y81X, 343delG, 457delT, 629delG, L295P, 926-927delTG, 1130delA, 1141-1155del15, and E428X).
Consistent with the patient's mild clinical phenotype, the I439S mutation conferred intermediate levels of repressor activity of DAX-1 when compared with mutations associated with classic AHC.
Our objective was to identify DAX1 mutations in a series of families, to determine the types of mutations resulting in AHC and to locate single-amino-acid changes in a DAX1 structural model.
X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis.
We analyzed the DAX-1 gene from seven patients in six kindreds with X-linked AHC and identified one frameshift mutation, two missense mutations, and three deletion mutations.
All AHC patients over 14 years old and with only point mutations in DAX-1 were also diagnosed with HHG, confirming that the DAX-1 gene is responsible for both X-linked AHC and HHG.