Neuroserpin mutation S52R causes neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy

Mutations in the Neuroserpin gene have been reported to cause familial pres enile dementia. We describe a new family in which the S52R Neuroserpin muta tion is associated with progressive myoclonus epilepsy in 2 siblings. The p roband presented myoclonus and epilepsy at age 24, his brother and mother p resented a similar disorder when they were 25. A clinical diagnosis of prog ressive myoclonus epilepsy was made on the proband and his brother. Skin an d liver biopsies did not reveal the presence of cytological alterations in the proband. His neurological status worsened over the subsequent 19 yr dur ing which he became demented and had uncontrollable seizures. He died at 43 yr of age from aspiration pneumonia. Neuropathologically, eosinophilic bod ies, which were positive for periodic acid-Schiff and immunoreactive with a ntibodies against human neuroserpin, were present in the perikarya and cell processes of the neurons. They were found in large numbers in the cerebral cortex and substantia nigra and to a lesser extent, in most subcortical gr ay areas, spinal cord, and dorsal root ganglia. By electron microscopy, the intracytoplasmic bodies were contained within the membranes of the rough e ndoplasmic reticulum. Occasionally neuroserpin immunopositivity was seen th roughout the cytoplasm, even without the presence of well-defined bodies. O ur study characterizes for the first time the neuropathologic phenotype ass ociated with hereditary progressive myoclonus epilepsy caused by the S52R N euroserpin mutation.