Elimination of the native structure and solubility of the hVAPB MSP domain by the Pro56Ser mutation that causes amyotrophic lateral sclerosis.

The Pro56Ser mutation in the human VAPB MSP domain causes a familial amyotrophic lateral sclerosis. Here we present the first structural investigation of both wild-type and Pro56Ser mutant MSP domains. The results reveal that the wild-type MSP domain is well-folded at neutral pH but can undergo acid-induced unfolding reversibly.

Genetic analysis of SCA 2 and 3 repeat expansions in essential tremor and atypical Parkinsonism.

Anecdotal reports suggest that patients with spinocerebellar ataxia (SCA 2) patients can present with postural tremor with ataxia. We determined the prevalence of SCA2 and SCA3 mutations in a cohort of ET and atypical Parkinsonism patients. A total of 277 subjects comprising of 177 ET and 100 atypical Parkinsonism were examined.