Sibling cases of Addison's disease caused by DAX-1 gene mutations.
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.
Sekiguchi
Yoshihiro
Y
Division of Endocrinology, Ohme Municipal General Hospital, Tokyo.
Hara
Yoshihito
Y
Matsuoka
Hiroshi
H
Hayashi
Yoshiki
Y
Katsumata
Noriyuki
N
Hirata
Yukio
Y
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
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins