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Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia
Gaia Skibinski1, Nicholas J Parkinson, Jeremy M Brown
1MRC Prion Unit, Institute of Neurology, University College London, London, UK.
Nature Genetics
|July 26, 2005
Summary
A mutation in CHMP2B causes frontotemporal dementia (FTD) by disrupting mRNA splicing. This finding links the endosomal ESCRTIII complex to neurodegenerative diseases like FTD.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Frontotemporal dementia (FTD) is a neurodegenerative disorder.
- Autosomal dominant FTD linked to chromosome 3 (FTD3) has been previously identified in a large Danish pedigree.
Purpose of the Study:
- To identify the genetic cause of FTD in the FTD3 pedigree.
- To investigate the role of the endosomal ESCRTIII complex in FTD pathogenesis.
Main Methods:
- Genetic analysis of affected individuals from the Danish pedigree.
- mRNA splicing analysis in tissue samples.
- Identification and characterization of CHMP2B mutations.
Main Results:
- A mutation in the CHMP2B gene was identified in the FTD3 pedigree, leading to aberrant mRNA splicing.
- An additional missense mutation in CHMP2B was found in an unrelated FTD patient.
- CHMP2B encodes a component of the endosomal ESCRTIII complex.
Conclusions:
- Aberrant function of the endosomal ESCRTIII complex due to CHMP2B mutations can cause frontotemporal dementia.
- This study implicates the endosomal ESCRTIII complex in the molecular mechanisms underlying FTD and other neurodegenerative diseases.