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Kennedy Disease (SBMA)

A non-lethal spinal bulbar muscular atrophy, sensory deficiency, frequently with gynecomastia and impotence expressed primarily in adults. The recessive gene was mapped to Xq12. The basic defect is a CAG repeat increase (11-33 CAG in normal→38-66 in SBMA) within the first exon of the androgen receptor (AR) in the spinal cord, brains stem and sensory neurons. Glucocorticoid receptor (GR) localizes the repeat into the nucleus. Deletion or mutation in the C-terminal of GR suppressed aggregation and nuclear localization. Surprisingly mutation in the DNA-binding N-terminal domain increased aggregation and