Thirteen novel mutations in the NR0B1 (DAX1) gene as cause of adrenal hypoplasia congenita.
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.
Krone
Nils
N
Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Schleswig-Holstein (Campus Kiel), Kiel, Germany. krone@pediatrics.uni-kiel.de
Riepe
Felix Günther
FG
Dörr
Helmuth-Günther
HG
Morlot
Michel
M
Rudorff
Karl-Heinz
KH
Drop
Stenvert L S
SL
Weigel
Johannes
J
Pura
Mikulas
M
Kreze
Alexander
A
Boronat
Mauro
M
de Luca
Filippo
F
Tiulpakov
Anatoly
A
Partsch
Carl-Joachim
CJ
Peter
Michael
M
Sippell
Wolfgang G
WG
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*
D018389:Codon, Nonsense; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins