Novel frameshift mutation of the NR0B1(DAX1) in two tall adult brothers.

Abstract	NR0B1 (nuclear receptor subfamily 0, group B, member 1) is a transcription factor encoded by DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) responsible for the development and maintenance of the steroidogenic tissues. In humans the DAX1 mutations cause congenital adrenal hypoplasia (AHC) and hypogonadotropic hypogonadism (HHG) in boys. Here we report two brothers who were assessed by endocrinologist at the age of 51 and 43 because of their serious osteoporosis. They had been substituted with prednisolone since the age of 4 and 9 years because of their primary adrenal insufficiency (PAI). Due to their late puberty caused by HHG at the age of 16 and 17 years their heights were - 3.1 and - 3.3 SD, but then they had a significant growth during their adulthood and reached the + 1.85 SD and + 3.78 SD respectively. During this period, they received glucocorticoid supplementation, but the treatment of their HHG was inadequate. At the age of 51 and 43 years insulin tolerance test (ITT) and gonadotropin releasing hormone (GnRH) test confirmed their PAI and HHG. Genetic test performed at this time revealed a novel, four nucleotides deletion (del.586-571c.GGGC or 572-575c.GGGC) of DAX1 gene. The two brothers with AHC and HHG caused by a novel DAX1 mutation, reached tall final heights, despite of the disadvantageous prednisolone treatment during their childhood. We assume that the long-term lack of the sexual hormone substitution was a significant reason of their above average height as well as their serious osteoporosis.
Authors	Rita Bertalan, Zsuzsa Bencsik, Piroska Mezei, Zsolt Vajda, Henriett Butz, Attila Patócs
Journal	Molecular biology reports (Mol Biol Rep) Vol. 46 Issue 4 Pg. 4599-4604 (Aug 2019) ISSN: 1573-4978 [Electronic] Netherlands
PMID	31280422 (Publication Type: Case Reports, Journal Article)
Chemical References	DAX-1 Orphan Nuclear Receptor NR0B1 protein, human
Topics	Addison Disease (genetics) Adult DAX-1 Orphan Nuclear Receptor (genetics, metabolism) Frameshift Mutation Humans Hypoadrenocorticism, Familial (genetics) Hypogonadism (genetics) Male Middle Aged Sexual Maturation Siblings

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