An atypical kindred with X-linked adrenal hypoplasia congenita, normal puberty, and normal Dax-1 promoter and coding sequence

We report a Chinese kindred with an atypical sex-linked form of isolated ad renal hypoplasia without hypogonadotropic hypogonadism, Evidence of sex lin kage was supported by DNA analysis using three polymorphic markers from the X-chromosome: a restriction fragment length polymorphism 200 kb centromeri c of the DAX-1 gene, a tetranucleotide repeat marker in the DAX-1 promoter (DAX-P), and a microsatellite in the Duchenne muscular dystrophy locus (3'- 19), This pedigree therefore presents the novel phenotype of sex-linked hyp oadrenalism without hypogonadotropic hypogonadism, with evidence of possibl e linkage to the DAX-1 gene. However, all three affected individuals were e xamined for mutations in the DAX-1 gene, and found to have no sequence anom alies in the coding region, splice sites or 5' non-coding region, This pres entation may be due to a defect in the DAX-1 gene outside its known coding region, possibly modulated by functional polymorphisms at other loci, and/o r environmental effects, or to a defect in a novel gene on the X chromosome which selectively influences adrenal development.