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.
A careful analysis of the pedigree of this family lead to the recognition of an X-linked inheritance pattern, with subsequent confirmation in a female heterozygous carrier of a DAX1 missense mutation c.1274G>T, (p.Arg425Ile).The diagnosis of this condition remains challenging in a developing country, since the manifestations of AHC overlap with those of the much more frequently occurring infections; darkening of the skin is difficult to evaluate and there is a lack of access to routine endocrinological testing.
Here, an asymptomatic father and his late-onset AHC daughter were both shown to share a novel DAX1 mutation (C200W), the first missense mutation identified in the hinge region of DAX1.