title: X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis.
abstract: X-linked congenital adrenal hypoplasia (AHC) is a developmental disorder of the human adrenal gland that results in profound hormonal deficiencies, which are lethal if untreated. Hypogonadotropic hypogonadism (HHG) is frequently associated with this disorder. The gene (DAX-1) responsible for the disease has recently been isolated. It encodes a protein with large similarity to members of the nuclear hormone receptor superfamily. Several different mutations in this gene have been found in patients suffering from AHC. We have identified a missense mutation (N440I) in three patients with AHC and HHG, all belonging to a large Greenlandic family. A total of 42 individuals has been tested for this mutation. We have diagnosed 10 women as carriers, and have excluded 22 women with a 25-50% risk from being carriers, emphasizing the rapid impact of molecular genetic techniques.
authors.affiliation: Department of Clinical Genetics, Juliane Marie Center, University Hospital, Rigshospitalet 4062, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
authors.forename: S
authors.initials: S
authors.lastname: Blichfeldt
authors.forename: J
authors.initials: J
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D000309:Adrenal Insufficiency / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001827:Body Height; D002675:Child, Preschool; D057137:DAX-1 Orphan Nuclear Receptor; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D006116:Greenland; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D007006:Hypogonadism / Q000235:genetics*; D007223:Infant; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins; D013739:Testosterone / Q000627:therapeutic use; D014157:Transcription Factors / Q000235:genetics*; D014960:X Chromosome
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D017931:DNA Primers; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors; D013739:Testosterone; D005438:Fludrocortisone; D006854:Hydrocortisone