X-linked muscular atrophy and the androgen receptor.
X-linked muscular atrophy is a form of adult-onset, usually slowly progressive spinal and bulbar motor neuron degenerative disease that is uniquely associated with male hypogonadism. The mutation responsible for this syndrome is expansion of the trinucleotide repeat-cytosine (C), adenine (A), guanine (G)-in a 5'-translated portion of the androgen receptor (AR) gene from a normal, polymorphic length of n = 11-31 to n >/= 40. The resulting androgen receptor (AR) protein has an expanded polyglutamine tract in its NH(2)-terminal modulatory domain, and is postulated to lose a basic, intrinsic function that causes a mild form of androgen insensitivity; however, almost certainly, it also gains a novel, extrinsic function that is selectively neuronotoxic. The unexplained mechanism that culminates in this form of neuronspecific death is the prototype for three different adult-onset neuronopathies that are caused by (CAG)(n) expansions in other genes.
Trifiro
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Lady Davis Institute for Medical Research, Departments of Medicine, Biology and Human Genetics, McGill University, Montreal, Quebec H3T 1E2, Canada.
Kazemi-Esfarjani
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Pinsky
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