The neuropathology and clinical phenotype of FTD with <Emphasis Type="Italic">progranulin</Emphasis> mutations |
| |
Authors: | Ian R A Mackenzie |
| |
Institution: | (1) Department of Pathology, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, BC, Canada, V5Z 1M9 |
| |
Abstract: | Mutations in the progranulin gene (PGRN), on chromosome 17q21, have recently been identified as a major cause of familial frontotemporal dementia (FTD). These cases
have a characteristic pattern of neuropathology that is a distinct subtype of frontotemporal lobar degeneration with ubiquitinated
inclusions (FTLD-U), with lentiform neuronal intranuclear inclusions being a consistent feature. There is no abnormal accumulation
of PGRN protein in the brain and immunohistochemical and biochemical analysis indicates that the ubiquitinated pathological
protein is TDP-43. In these families, FTD is inherited in an autosomal dominant fashion with high penetrance. The clinical
phenotype is usually a combination of behavioural abnormality and language disturbance that is most often a form of primary
progressive aphasia. Mild parkinsonism is common but motor neuron disease is notably rare. Marked variation in the disease
course and clinical features are common, not only between families with different mutations, but also within individual families.
This degree of clinical variability makes it difficult to predict which cases of familial FTD will turn out to have a PGRN
mutation. |
| |
Keywords: | Progranulin Frontotemporal dementia TDP-43 |
本文献已被 PubMed SpringerLink 等数据库收录! |
|