Extended FTLD pedigree segregating a Belgian GRN -null mutation: neuropathological heterogeneity in one family

摘要: In this paper, we describe the clinical and neuropathological findings of nine members Belgian progranulin gene (GRN) founder family. family, loss-of-function mutation IVS1 + 5G > C was identified in 2006. 2007, a description carriers published that revealed heterogeneity among carriers. We report our comparison data with characteristics other GRN mutations as well frontotemporal lobar degeneration (FTLD) syndromes, present review literature. For each case, standardized sampling staining were performed to identify proteinopathies, cerebrovascular disease, hippocampal sclerosis. The substrate studied family compatible all cases transactive response DNA-binding protein (TDP) proteinopathy type A, expected. Additionally, most presented also primary age-related tauopathy (PART) or mild Alzheimer’s disease (AD) changes, one case had extensive Lewy body pathology. An additional finding presence cerebral small vessel changes every patient Our show not only has an exclusive association FTLD-TDP A but proteinopathies can occur should be looked for. Because penetrance rate phenotype is age-dependent, further research required investigate role co-occurring pathologies such AD, PART, disease.