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 adrenal hypoplasia without hypogonadotropic hypogonadism. Evidence of sex linkage was supported by DNA analysis using three polymorphic markers from the X-chromosome: a restriction fragment length polymorphism 200 kb centromeric 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 hypoadrenalism without hypogonadotropic hypogonadism, with evidence of possible linkage to the DAX-1 gene. However, all three affected individuals were examined for mutations in the DAX-1 gene, and found to have no sequence anomalies in the coding region, splice sites or 5' non-coding region. This presentation 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/or environmental effects, or to a defect in a novel gene on the X chromosome which selectively influences adrenal development.
Loke
K Y
KY
Department of Paediatrics, National University of Singapore.
Poh
K S
KS
Walker
A P
AP
Tan
J A
JA
Tay
A H
AH
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000328:Adult; D002648:Child; D002681:China; D057137:DAX-1 Orphan Nuclear Receptor; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D015247:Deoxyribonuclease HindIII; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D011627:Puberty; D012326:RNA Splicing; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D014960:X Chromosome
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D015247:Deoxyribonuclease HindIII