According to our knowledge, this is the first case in the literature with NR0B1 mutation causing adrenal insufficiency with coexistent positive adrenal antibodies.
Nevertheless, genetic testing for NR0B1 mutations is indicated if there is a suspicion of an X-linked adrenal insufficiency in order to proceed with the appropriate therapy and genetic counseling.
Here, we report a newborn who had a novel hemizygous frameshift mutation in DAX1(c.543delA) and presented with primary adrenal failure that was initially misdiagnosed as congenital adrenal hyperplasia.
We report a girl with a de novo deletion at Xp21.2 on the maternal chromosome, including DAX1, the GK gene and 3' end of the dystrophin gene, who presented with salt losing adrenal insufficiency and moderate developmental delay, but relatively mild features of muscular dystrophy.
We describe a 21-year-old 46,XY female manifesting primary amenorrhea, a small immature uterus, gonadal dysgenesis, and notably absent adrenal insufficiency with a submicroscopic (257 kb) deletion upstream of NR0B1.
We report a new DAX1 gene mutation in a family with two affected members: one with neonatal adrenal insufficiency, and a sibling with adrenal hypoplasia and sudden death at 3 years old.
Mutations in the DAX1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita (AHC) critical region on the X chromosome gene 1; NR0B1) cause X-linked AHC, a disease characterized by primary adrenal failure in infancy and hypogonadotropic hypogonadism.
Mutations in DAX1 [dosage-sensitive sex reversal-adrenal hypoplasia congenita (AHC) critical region on the X chromosome gene 1; NR0B1] cause X-linked AHC, a disease characterized by primary adrenal failure in infancy or childhood and reproductive abnormalities later in life.
This case demonstrates that partial loss-of-function mutations in DAX1 can present with hypogonadotropic hypogonadism and covert adrenal failure in adulthood.
All DAX-1 missense mutant constructs showed marked loss of repressor function, with the exception ofI439S, a mutation previously shown to be associated with delayed-onset adrenal failure and incomplete hypogonadotropic hypogonadism.
This pedigree therefore presents the novel phenotype of sex-linked hypoadrenalism without hypogonadotropic hypogonadism, with evidence of possible linkage to the DAX-1 gene.
This study suggests that mutations in DAX1 are unlikely to be a common cause of HH or pubertal delay in the absence of a concomitant history of adrenal insufficiency.