Deng et al. (2011) identified a 5-generation family with ALS15 including 19 affected individuals. The disease was transmitted in a dominant fashion with reduced penetrance in females. Deng et al. (2011) also identified 4 other unrelated families with ... Deng et al. (2011) identified a 5-generation family with ALS15 including 19 affected individuals. The disease was transmitted in a dominant fashion with reduced penetrance in females. Deng et al. (2011) also identified 4 other unrelated families with ALS15 and obtained clinical data from a total of 40 individuals, including 35 patients and 5 obligate carriers. Penetrance was approximately 90% by age 70 years. The age of onset of disease ranged from 16 to 71 years. There was a significant difference in the age of onset between male and female patients, with male patients having an earlier age of onset (33.9 +/- 14.0 years vs 47.3 +/- 10.8 years, P = 0.003, 2-tailed Student's t-test). However, there were no statistically significant differences in the duration of the disease (43.1 +/- 42.1 months vs 48.5 +/- 19.9 months, P = 0.61). Eight patients manifested both ALS and dementia. Dementia in these patients was similar to frontotemporal lobar type (see 600274), including abnormalities in both behavior and executive function. The dementia was progressive and eventually global in most ALS/dementia patients. In some cases the dementia preceded motor symptoms, but all patients eventually developed motor disability. Pathologic analysis of spinal cord autopsy samples from 2 patients revealed axonal loss in the corticospinal tract, loss of anterior horn cells, and astrocytosis in the anterior horn of the spinal cord.
Based on expression profile, function, structure, and potential relevance of their encoded proteins, Deng et al. (2011) selected 41 genes for sequencing within the ALS15 candidate region. They identified 5 different proline substitutions in the PXX repeat domain ... Based on expression profile, function, structure, and potential relevance of their encoded proteins, Deng et al. (2011) selected 41 genes for sequencing within the ALS15 candidate region. They identified 5 different proline substitutions in the PXX repeat domain of UBQLN2 as causative of ALS15 in 5 unrelated families.