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The Genetic and Pathological Classification of Familial Frontotemporal Dementia
Huw R. Morris, MRCP;
M. Nadeem Khan, MSc;
John C. Janssen, MRCP;
Jeremy M. Brown, MD;
Jordi Perez-Tur, PhD;
Matthew Baker, BSc;
Mehmet Ozansoy, MSc;
John Hardy, PhD;
Michael Hutton, PhD;
Nicholas W. Wood, PhD;
Andrew J. Lees, MD;
Tamas Revesz, MD;
Peter Lantos, MD;
Martin N. Rossor, MD
Arch Neurol. 2001;58:1813-1816.
Background Frontotemporal dementia (FTD) is an important
cause of neurodegenerative dementia, particularly in younger patients.
TAU has been identified as the gene responsible for FTD linked
to chromosome 17, but it is likely that there is pathological and
genetic heterogeneity among families with FTD.
Objective To explore the genetic and pathological basis of
familial FTD.
Design Clinical case series with genetic analysis of each
family, and pathological confirmation of diagnosis where possible.
Setting Specialist dementia research group, particularly
recruiting patients with young-onset dementia.
Patients Twenty-two families with an index member with FTD,
meeting Lund-Manchester criteria, and a family history of other
affected members with dementia were ascertained.
Results Half of the families had mutations in the TAU
gene (TAU exon 10 +14, +16, and P301S), and pathological
diagnoses were available in 17 of 22 families. Three main pathological
diagnoses were made: FTD with neuronal and glial tau deposition, FTD
with ubiquitin inclusions, and FTD with neuronal loss and spongiosis
but without intracellular inclusions. No cases of familial Pick disease
were identified. With the use of the pathological diagnoses, each
family with FTD with neuronal and glial tau deposition had a
TAU mutation, whereas TAU mutations were not
identified in families in the other 2 diagnostic groups.
Conclusions This study illustrates the value of
TAU sequencing in FTD and suggests that around one half of
individuals with familial FTD have TAU mutations and dementia
with tau pathological findings. Furthermore, these data suggest that
there are at least 2 additional genes to be identified among families
with autosomal dominant FTD.
From the Neurogenetics Section (Drs Morris and Wood), Dementia Research
Group (Drs Janssen and Rossor), and Department of
Neuropathology (Dr Revesz), Institute of Neurology, and Reta Lila
Weston Institute of Neurological Studies (Drs Morris and Lees and Mr
Ozansoy), University College London, London, England; MRC
Brain Bank, Department of Neuropathology, Institute of Psychiatry,
London (Mr Khan and Dr Lantos); Department of Neurology, Addenbrooke's
Hospital, Cambridge, England (Dr Brown); Unitat de Genetica Molecular,
Institut de Biomedicina de Valencia-CSIC, Valencia, Spain (Dr
Perez-Tur); and Neurogenetics Laboratory, Mayo Clinic Jacksonville,
Jacksonville, Fla (Mr Baker and Drs Hardy and Hutton)
Corresponding author and reprints: Martin N. Rossor, MD,
Dementia Research Group, Institute of Neurology, Queen Square, London
WC1N 3BG, England (e-mail: m.rossor{at}dementia.ion.ucl.ac.uk).
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