title: X-linked muscular atrophy and the androgen receptor.
abstract: 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.
authors.affiliation: Lady Davis Institute for Medical Research, Departments of Medicine, Biology and Human Genetics, McGill University, Montreal, Quebec H3T 1E2, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Trifiro
authors.forename: P
authors.initials: P
authors.lastname: Kazemi-Esfarjani
authors.forename: L
authors.initials: L
authors.lastname: Pinsky