X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N440I) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis
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- Schwartz, M., Blichfeldt, S. & Müller, J. Hum Genet (1996) 99: 83. doi:10.1007/s004390050316
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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.