Novel deletion mutations of the DAX1 (NR0B1) gene in two Taiwanese families with X-linked adrenal hypoplasia congenita.
OBJECTIVE
To analyze the DAX1 (NROB1) gene in Taiwanese families with adrenal hypoplasia congenita.


METHODS
Two unrelated Taiwanese patients were followed up at our pediatric endocrine clinic. Both patients presented with adrenal crisis. One patient entered puberty spontaneously. However, arrest of puberty was noted in the following years and hypogonadotropic hypogonadism was confirmed by GnRH test. The other patient was still prepubertal. Sequencing of the DAX1 (NROB1) gene was carried out in both patients and their respective family members.


RESULTS
Two different novel mutations were identified. The first patient had one base (G) deletion at nucleotide 159, resulting in a frame-shift and a premature stop codon at position 84. The other patient had one base (G) deletion at nucleotide 831, leading to a frameshift and a premature stop codon at position 371. Family studies revealed that their mothers and sisters were heterozygotes for the mutations while their maternal grandmothers did not carry the mutations.


CONCLUSIONS
Two Taiwanese patients with adrenal hypoplasia congenita were detected to have novel mutations of the DAX1 (NR0B1) gene. Family studies suggested that such mutations resulted from de novo mutation of the DAX1 (NROB1) gene in their mothers. These data indicate that molecular analysis of the DAX1 (NR0B1) gene is important for the diagnosis and genetic counseling of children with primary adrenal insufficiency.
Tsai
Wen-Yu
WY
Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. wenyu@ha.mc.ntu.edu.tw
Tung
Yi-Ching
YC
D000311:Adrenal Glands / Q000002:abnormalities*; D000309:Adrenal Insufficiency / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D000328:Adult; D001483:Base Sequence; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013624:Taiwan
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins