SPINAL AND BULBAR MUSCULAR-ATROPHY - A TRINUCLEOTIDE-REPEAT EXPANSIONNEURODEGENERATIVE DISEASE

Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset motor neuronopathy that is caused by expansion of a trinucleotide (CAG ) repeat in the androgen-receptor gene. The length of this repeat vari es as it is passed down through SBMA families, and correlates inversel y with the age of onset of the disease. The motor-neuron degeneration that occurs in this disease is probably caused by a toxic gain of func tion in the androgen-receptor protein. Subsequent to the identificatio n of the mutation in SBMA, other inherited neurodegenerative diseases have been found to be caused by the expansion of CAG repeats in the co ding regions of other genes. Because these diseases probably share a c ommon pathogenesis, investigation of SBMA might help to determine a ge neral mechanism of neuronal degeneration.