Genetical, morphological, and functional analysis of CHMP2B in a patient of familial FTD

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The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) associated to chromosome 3 in a Danish FTLD family (FTD-3). We report a Japanese family of FTD-3 that developed FTLD in 6members of 3 successive generations. Interestingly, 4 members of 2 successive generations had gastric cancer, and FTLD and gastric cancer cosegregated in the two family members. CHMP2B encode a component of the heteromeric ESCRT-III complex (endosomal sorting complex required for transport III). Dysfunction of the endosomal systems may lead FTLD and cancer.We observed ubiquitin-positive and TDP-43-negative neuronal intracytoplasmic inclusions as previously reported. We could not find any mutation in the CHMP2B gene, however, we observed shorten splicing variant of the m-RNA. The variant showed modified amino acid sequence in the C-terminal.