In affected individuals from an American family of English origin with a prion disease clinically similar to Gerstmann-Straussler disease (GSD; 137440), Cervenakova et al. (1999) and Butefisch et al. (2000) identified an A-to-G transition in the PRNP gene, resulting in a his187-to-arg (H187R) substitution in the third alpha-helical segment of the protein. Six unaffected family members did not have the mutation. Median age at disease onset was 42 years (range 33 to 50 years), characterized by ataxic gait, dysarthria, behavioral abnormalities, and cognitive decline. All of the patients had cerebellar atrophy, 3 developed myoclonic jerks, and 2 developed seizures. Only 1 patient showed intermittent triphasic periodic synchronous waves on EEG. Median disease duration was 12 years. Brain biopsy of 1 patient showed round or elongated PrP 'curly' granular deposits in the cortex without spongiform changes. No autopsies were performed.
Hall et al. (2005) identified the H187R mutation in affected members of a family with dementia, cerebellar signs, and extrapyramidal signs. Four patients developed neuropsychiatric symptoms (see 606688) in childhood or adolescence, including kleptomania, pyromania, and impulsivity. Age at onset of dementia ranged from 20 to 44 years. Neuropathologic examination of 4 patients showed moderate to severe cerebral atrophy, without other distinctive features.
