Introduction Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is an autosomal-dominant neurodegenerative disease caused by mutations in the proteinase inhibitor 12 gene (PI12; SERPINI1), located on chromosome 3q26 . The PI12 gene encodes the protein neuroserpin, a protein of 54–60 kDa that is expressed predominantly by neurons of the central and peripheral nervous system. Neuroserpin is a serine protease inhibitor that inhibits tissue-type plasminogen activator. Mutations in the PI12 gene lead to the formation of neuroserpin intracytoplasmic inclusion bodies (IBs), called Collins bodies, within neurons [1–3]. Accumulation of polymers composed of the mutant neuroserpin protein in IBs seems to lead to a gain of a toxic function by the mutant neuroserpin; however, loss of the normal function of neuroserpin may also contribute to the pathology, with these two mechanisms acting together to lead to the progression of the disease and neurodegeneration. In patients with FENIB, neuroserpin IBs may be found in the brain and the spinal cord. They may be also found outside the central nervous system in neurons of the dorsal root ganglion but not in cells of other organ systems [1–6]. Clinical phenotypes The onset of clinical signs and symptoms of FENIB may be highly variable depending on the specific mutation [1–8]. Patients carrying a mutation that causes high instability of neuroserpin have an earlier onset of the disease, more severe clinical manifestations, a shorter life expectancy and numerous IBs when compared with patients with a more stable mutant form of neuroserpin. The disease, which occurs equally in males and females, may present with progressive myoclonus epilepsy, focal or generalized seizures, dysarthria, tremors and dementia. Affected individuals consistently demonstrate deficits in areas associated with frontal-lobe processes. The course of the disease can be quite long, exceeding 10 years in some cases. Prior to the onset of neurological signs, mutation carriers have almost intact cognition, with the exception of restricted attention, concentration and oral fluency .
ASJC Scopus subject areas