Premium
Thirteen novel mutations in the NR0B1 ( DAX1 ) gene as cause of adrenal hypoplasia congenita
Author(s) -
Krone Nils,
Riepe Felix Günther,
Dörr HelmuthGünther,
Morlot Michel,
Rudorff KarlHeinz,
Drop Stenvert L.S.,
Weigel Johannes,
Pura Mikulas,
Kreze Alexander,
Boronat Mauro,
de Luca Filippo,
Tiulpakov Anatoly,
Partsch CarlJoachim,
Peter Michael,
Sippell Wolfgang G.
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9331
Subject(s) - biology , adrenal insufficiency , primary adrenal insufficiency , nonsense mutation , genetics , mutation , gene , endocrinology , medicine , stop codon , missense mutation
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.269lowbar;270dup, c.421lowbar;422dup, c.895lowbar;896dup, c.989dup, c.999lowbar;1000dup), and five deletions (c.483del, c.745lowbar;746del, c.734lowbar;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. © 2005 Wiley‐Liss, Inc.