engleski

Frontotemporal lobar degeneration with ubiquitin-positive inclusions and progranulin mutation in two kindreds

Clinically, cases of frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) present with behavioral and language problems and may also have motor neuron disease. Neuropathologically, there is frontal and temporal lobe atrophy, neuronal loss, microvacuolation, and gliosis in affected areas. Recently, mutations in the progranulin (PGRN)gene were linked to chromosome 17q21. The majority of these families with PGRN mutations contain ubiquitin and TDP-43 positive inclusions. Used methods were Immunohistochemistry ; DNA sequencing. We report on two FTLD-U kindred: 1. Hereditary Dysphasic Disinhibition Dementia-2 (HDDD2)with prominent changes in behavioral and language deficits with a missense mutation, Ala-9-Asp within the signal peptide, and 2. HDDD1, another kindred with personality changes, disinhibition, non-fluent dysphasia followed by memory loss. There is a novel pathogenic PGRN mutation c.5913 A>G in the HDDD1 kindred. Both, HDDD2 and HDDD1 kindred are FTLD-U with PGRN mutations. Different mutations in the same PGRN gene cause clinical and neuropathological heterogeneity in FTLD-U.

fontotemporal dementia; ubiquitin; progranulin

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