A de novo mutation of DAX1 in a boy with congenital adrenal hypoplasia without hypogonadotropic hypogonadism.

Abstract

We report the case of a 12-year-old boy with a de novo mutation in the DAX1 gene (for dosage-sensitive sex reversal, congenital adrenal hypoplasia critical region on the X chromosome, gene 1; also called NROB1). He was born at term, Addison's disease was diagnosed at 8 years with a salt-wasting syndrome, and then hydrocortisone substitution was taken; the child continued to develop normally. A reoccurrence of salt-wasting syndrome usually happened after an episode of an abrupt withdrawal of hydrocortisone substitution. Because of adrenal insufficiency without hypogonadotropic hypogonadism, he came to the clinic at 12 years of age and hypoplasia of adrenal glands was found by MRI scans. We proposed the diagnosis of congenital adrenal hypoplasia in this patient and identified a hemizygous mutation (c.999_1000insCTCA, p.Leu335ThrfsX389) in exon 1 of the DAX1 gene. To our knowledge, it is a de novo mutation that leads to a frame-shift, a premature stop codon. In conclusion, it is very important to identify mutation in the DAX1 gene for a boy with adrenal insufficiency of unknown etiology.

• Authors: Chun Lin Wang, Zhu Wei Fen, Li Liang
• Journal: Journal of pediatric endocrinology & metabolism : JPEM (J Pediatr Endocrinol Metab) Vol. 27 Issue 3-4 Pg. 343-7 (Mar 2014) ISSN: 2191-0251 [Electronic] Germany
• PMID: 24197767 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DAX-1 Orphan Nuclear Receptor
• DNA Primers
• NR0B1 protein, human

Topics

• Adrenal Hyperplasia, Congenital (complications, genetics)
• Adrenal Insufficiency
• Base Sequence
• Child
• DAX-1 Orphan Nuclear Receptor (genetics)
• DNA Primers
• Frameshift Mutation
• Genetic Diseases, X-Linked (complications, genetics)
• Humans
• Hypoadrenocorticism, Familial
• Hypogonadism (complications)
• Male
• Mutation, Missense
• Reverse Transcriptase Polymerase Chain Reaction