Ky. Loke et al., An atypical kindred with X-linked adrenal hypoplasia congenita, normal puberty, and normal Dax-1 promoter and coding sequence, J PED END M, 13(1), 2000, pp. 29-36
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.