The theme of this week's presentation and journal club will be the moecluar pathogenesis of the muscular dystrophies. The major issues to be discussed will concern questions that are directly relevant to virtually all neurodegenerative diseases. Specifically, we will discuss the question of how mutations in different genes may lead to the same clinical phenotype (in this case, a muscular dystrophy). This leads to the question as to whether or not there are final common pathophysiologic pathways leading to this phenotype, and how the biochemical consequences of mutations in different genes (or biochemical changes underlying "sporadic", i.e. non-hereditary, cases of the same phenotypes) might converge on these pathways. Secondary issues that will be raised by the specific papers to be discussed the
following week is the range of pathophysiological mechanisms that may operate in autosomal dominant degenerative disorders, and the range of pathophysiological mechanisms that may operate in trinucleotide repeat diseases.

The papers for presentation by Alyssa Brewer and Rory Sayres will be:

Galbiati F, Volonte D, Minetti C, Chu JB, Lisanti MP (1999) Phenotypic behavior of caveolin-3 mutations that cause autosomal dominant limb girdle muscular dystrophy (LGMD-1C). Retention of LGMD-1C caveolin-3 mutants within the golgi complex. J Biol Chem., 274: 25632-41.

Mankodi A, Logigian E, Callahan L, McClain C, White R, Henderson D, Krym M, Thornton CA (2000) Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science, 289: 1769-73.