Age-dependent differences in androgen binding affinity in a family with spinal and bulbar muscular atrophy

Abstract

Objectives: To investigate androgen receptor (AR) function in spinal and bulbar muscular atrophy (SBMA). Methods: A kindred was identified with five individuals carrying the AR gene CAG repeat expansion that causes SBMA. Androgen binding was measured in cultured genital skin fibroblasts from three affected individuals. One newborn, pre-symptomatic, individual showed normal androgen binding, but two older, symptomatic individuals showed a decrease in androgen binding affinity. This difference was not related to AR CAG repeat size, as all affected individuals in this kindred had 49 repeats (normal range 6-35). Post-mortem analysis in one subject confirmed the signs of androgen insufficiency in..