Diagnosis of X-linked Adrenal Hypoplasia Congenita by Mutation Analysis of the DAX1 Gene

Abstract

Molecular genetic and molecular cytogenetic techniques represent rapid and complementary approaches to the diagnosis of mutations in the DAX1 gene responsible for AHC and the associated HH. Specific diagnosis of the cause of adrenal insufficiency in these boys permits anticipatory management of the HH and prenatal counseling for parents of the affected child and other members of their families.

Hypogonadotropic hypogonadism in subjects with DAX1 mutations

“…1) (Reutens et al, 1999, Lin et al, 2006, Achermann et al, 2000, Muscatelli et al, 1994, Zanaria et al, 1994, Guo, Mason, Stone et al, 1995, Takahashi, Shoji, Haraguchi et al, 1997, Meloni, Cao and Rosatelli, 1996, Nakae, Abe, Tajima et al, 1997, Schwartz, Blichfeldt and Muller, 1997, Peter, Viemann, Partsch et al, 1998, Seminara, Achermann, Genel et al, 1999, Bassett, O’Halloran, Williams et al, 1999, Caron, Imbeaud, Bennet et al, 1999, Merke, Tajima, Baron et al, 1999, Tabarin, Achermann, Recan et al, 2000, Domenice, Latronico, Brito et al, 2001, Wiltshire, Couper, Rodda et al, 2001, Sekiguchi, Hara, Matsuoka et al, 2007, Bernard, Ludbrook, Queipo et al, 2006, Verrijn Stuart, Ozisik, de Vroede et al, 2007, Landau, Hanukoglu, Sack et al, 2010, Li, Liu, Zhang et al, 2010, Sykiotis, Hoang, Avbelj et al, 2010, Abe, Nakae, Yasoshima et al, 1999, Achermann, Meeks and Jameson, 2001, Ahmad, Paterson, Lin et al, 2007, Argente, Ozisik, Pozo et al, 2003, Balsamo, Antelli, Baldazzi et al, 2005, Brown, Scobie, Townsend et al, 2003, Calliari, Longui, Rocha et al, 2007, Frapsauce, Ravel, Legendre et al, 2011, Garcia-Malpartida, Gomez-Balaguer, Sola-Izquierdo et al, 2009, Guo, Burris, Zhang et al, 1996, Habiby, Boepple, Nachtigall et al, 1996, Hamaguchi, Arikawa, Yasunaga et al, 1998, Kinoshita, Yoshimoto, Motomura et al, 1997, Krone, Riepe, Dorr et al, 2005, Lam, Cheng, Poon et al, 2006, Mantovani, Ozisik, Achermann et al, 2002, Mericq, Ciaccio, Marino et al, 2007, Nakae, Tajima, Kusuda et al, 1996, Ozisik, Mantovani, Achermann et al, 2003, Salvi, Gomez, Fiaux et al, 2002, Tsai and Tung, 2005, Wang, Killinger and Hegele, 1999, Wu, Zhang, Zhou et al, 2011, Yanase, Takayanagi, Oba et al, 1996, Zhang, Guo, Wagner et al, 1998, Zhang, Huang, Anyane-Yeboa et al, 2001, Franzese, Brunetti-Pierri, Spagnuolo et al, 2005, Laissue, Copelli, Bergada et al, 2006, Okuhara, Abe, Kondo et al, 2008). After other known causes (i.e., congenital adrenal hyperplasia, CAH) have been excluded, it is estimated that as many as 50% of boys with idiopathic primary adrenal insufficiency may have mutations in DAX1 (…”

Longitudinal Evaluation of the Hypothalamic-Pituitary-Testicular Function in 8 Boys with Adrenal Hypoplasia Congenita (AHC) Due to NR0B1 Mutations

“…Boys carrying mutations in the NR0B1 gene develop adrenal failure (adrenal hypoplasia congenital, AHC) and showed impaired sexual development at puberty, followed by infertility. This impairment is due to the combination of hypogonadotropic hypogonadism (HH) [2], [3], [4] and a primary defect in spermatogenesis [5]. Male mice lacking Dax-1 are infertile due at least partly to blockage of the rete testis, with subsequent dilatation of the proximal efferent ductules [6].…”

X-linked adrenal hypoplasia congenita: a novel DAX1 missense mutation and challenges for clinical diagnosis in Africa

“…The DAX1 gene consists of two exons of 1,168 and 245 bp, respectively, separated by a 3,385 kb intron and codes for an atypical, 470-amino acid member of the orphan nuclear receptor superfamily [3,17]. DAX1 expression has been detected in the anterior pituitary, hypothalamic ventromedial nucleus, developing adrenal cortex, adult adrenal cortex, Sertoli and Leydig cells in the testis, and theca and granulosa cells in the ovary [2,10,17].…”