title: Sibling cases of Addison's disease caused by DAX-1 gene mutations.
abstract: We report two sibling cases of Addison's disease without any evidence of sexual precocity, adrenal hyperplasia, or autoimmune disease. The diagnosis of primary adrenocortical insufficiency was made at the age of 5 in the younger brother and at the age of 18 in the elder brother. The younger brother had been inactive during infancy and had diffuse skin pigmentation without abnormal external genitalia, while the elder brother had been healthy until the age of 17 when he noticed skin pigmentation and small testes. Both boys had delayed puberty due to hypogonadotropic hypogonadism. The diagnosis of adrenal hypoplasia congenita (AHC) was established by genetic analysis of DAX-1 gene (dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene 1) with the same single frameshift mutation (305delG). However, yet-uncharacterized epigenetic, nongenetic and/or genetic factors other than the DAX-1 gene may be responsible for the differential onset of AHC in these sibling cases.
authors.affiliation: Division of Endocrinology, Ohme Municipal General Hospital, Tokyo.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sekiguchi
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Hara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000224:Addison Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D035781:Siblings; D012880:Skin Pigmentation; D013737:Testis / Q000002:abnormalities
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins