title: Thirteen novel mutations in the NR0B1 (DAX1) gene as cause of adrenal hypoplasia congenita.
abstract: X-linked adrenal hypoplasia congenita (AHC) is a rare developmental disorder associated with primary adrenal insufficiency and combined primary and secondary male hypogonadism. It is caused by deletions or mutations of the NR0B1 (DAX1) gene encoding DAX1, an atypical orphan member of the nuclear receptor superfamily. The continuous molecular genetic analysis of male patients with primary adrenal insufficiency revealed 13 novel mutations within the coding region of the NR0B1 gene which are predicted to inactivate the DAX1 function. These were three nonsense mutations (c.312C>A, p.Cys104X, c.670C>T, p.Gln224X; and c.873G>A, p.Trp291X), five duplications (c.269_270dup, c.421_422dup, c.895_896dup, c.989dup, c.999_1000dup), and five deletions (c.483del, c.745_746del, c.734_740del, c.1092del, and c.1346del). All of the mutations resulted in a premature stop codon destroying the ligand binding domain of the predictive DAX1 protein.
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Schleswig-Holstein (Campus Kiel), Kiel, Germany. krone@pediatrics.uni-kiel.de
authors.forename: Nils
authors.initials: N
authors.lastname: Krone
authors.forename: Felix Günther
authors.initials: FG
authors.lastname: Riepe
authors.forename: Helmuth-Günther
authors.initials: HG
authors.lastname: Dörr
authors.forename: Michel
authors.initials: M
authors.lastname: Morlot
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Rudorff
authors.forename: Stenvert L S
authors.initials: SL
authors.lastname: Drop
authors.forename: Johannes
authors.initials: J
authors.lastname: Weigel
authors.forename: Mikulas
authors.initials: M
authors.lastname: Pura
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreze
authors.forename: Mauro
authors.initials: M
authors.lastname: Boronat
authors.forename: Filippo
authors.initials: F
authors.lastname: de Luca
authors.forename: Anatoly
authors.initials: A
authors.lastname: Tiulpakov
authors.forename: Carl-Joachim
authors.initials: CJ
authors.lastname: Partsch
authors.forename: Michael
authors.initials: M
authors.lastname: Peter
authors.forename: Wolfgang G
authors.initials: WG
authors.lastname: Sippell
mesh_terms: D000309:Adrenal Insufficiency / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D057137:DAX-1 Orphan Nuclear Receptor; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics*; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins