engleski

Frontotemporal dementia with ubiquitin-positive, tau-negative inclusions and progranulin mutation in two kindreds

Introduction: Frontotemporal dementia is the second most common form of dementia in people under the age of 65 years after Alzheimer’ s disease (AD), clinically and pathologically distinct from AD (Liscic et al. 2007). 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. The hallmark lesions of FTLD-U are: ubiquitin-positive, tau- and α -synuclein-negative inclusions. Recently, mutations in the progranulin (PGRN) gene were linked to chromosome 17q21 (Baker et al. 2006 ; Cruts et al. 2006). The majority of these families with PGRN mutations contain ubiquitin and TDP-43-positive inclusions. Progranulin is not a component of the inclusions (Neumann et al. 2006). Methods: Immunohistochemistry ; DNA sequencing. Results: We report on two FTLD-U kindreds: 1. Hereditary Dysphasic Disinhibition Dementia-2(HDDD2) with prominent changes in behavior and language deficits with a missense mutation, Ala-9-Asp within the signal peptide (Mukherjee et al. 2006), and 2. HDDD1, another Kindred with personality changes, disinhibition, nonfluent dysphasia followed by memory loss. There is a novel pathogenic PGRN mutation c.5913 A>G (IVS6-2 A>G) in the HDDD1 kindred (Behrens et al. 2007). Conclusion: Both, HDDD2 and HDDD1 kindreds are FTLD-U with PGRN mutations. Different mutations in the same PGRN gene cause clinical and neuropathological heterogeneity in FTLD-U. These important findings may provide a genetic and molecular basis for FTLD-U caused by PGRN mutations. References: 1.Liscic RM, et al. Arch Neurol 2007 ; 64:535-540. 2.Baker M, et al. Nature 2006 ; 442:916-919. 3.Cruts M, et al. Nature 2006 ; 442:920-924. 4.Mukherjee O, et al. Ann Neurol 2006 ; 60:314-322. 5.Behrens MI, et al. Alzheimer Dis Assoc Disord 2007 ; 21:1-7. 6.Neumann M, et al. Science 2006 ; 314: 130-133.

Frontotemporal dementia; HDDD1; HDDD2; progranulin; ubiquitin-positive inclusions

nije evidentirano