TY - JOUR
T1 - 17q-Linked Frontotemporal Dementia-Amyotrophic Lateral Sclerosis Without Tau Mutations with Tau and α-Synuclein Inclusions
AU - Wilhelmsen, Kirk C.
AU - Forman, Mark S.
AU - Rosen, Howard J.
AU - Alving, Loren I.
AU - Goldman, Jill
AU - Feiger, Jennie
AU - Lee, James V.
AU - Segall, Samantha K.
AU - Kramer, Joel H.
AU - Lomen-Hoerth, Catherine
AU - Rankin, Katherine P.
AU - Johnson, Julene
AU - Feiler, Heidi S.
AU - Weiner, Michael W.
AU - Lee, Virginia M.Y.
AU - Trojanowski, John Q.
AU - Miller, Bruce L.
PY - 2004/3
Y1 - 2004/3
N2 - Background: Frontotemporal dementia (FTD) is a clinically heterogeneous condition that can be associated with clinical manifestations of an extrapyramidal disorder or motor neuron disease. A range of histologic patterns has been described in patients with FTD. The most common familial form of this condition is caused by mutationsin the microtubule-associated protein tau gene (MAPτ) and is associated with neuronal or glial tau inclusions. Objectives: To determine the clinical, anatomic, and pathological features of San Francisco family A and to map the mutation responsible for disease in this family. Design: A systematic clinical, neuropsychologic, neuroimaging, and chromosome segregation analysis of San Francisco family A was performed. A pathological and biochemical assessment of a family member was made. Setting: Family study. Patients: San Francisco family A, with FTD, variable extrapyramidal symptoms, and prominent motor neuron disease. Afflicted family members donot have a MAPτ coding or splice regulatory sequence mutation, and the MAPτ is genetically excluded. Main Outcome Measures: Comparison of clinical, neuropsychologic, neuroimaging, and linkage findings of San Francisco family A with other familial forms of FTD and amyotrophic lateral sclerosis (ALS). Results: The most probable location for the mutation responsible for this condition is on chromosome arm 17q, distal to the MAPτ. All previously identified susceptibility loci for FTD and ALS are excluded. Autopsy findings from an afflicted family member show distinctive tau and α-synuclein inclusions. Another unique feature is that the insoluble tau protein consists predominantly of the 4R/0N isoform. Conclusion: The condition affecting members of San Francisco family A is clinically, pathologically, and genetically distinct from previous familial forms of FTD and ALS.
AB - Background: Frontotemporal dementia (FTD) is a clinically heterogeneous condition that can be associated with clinical manifestations of an extrapyramidal disorder or motor neuron disease. A range of histologic patterns has been described in patients with FTD. The most common familial form of this condition is caused by mutationsin the microtubule-associated protein tau gene (MAPτ) and is associated with neuronal or glial tau inclusions. Objectives: To determine the clinical, anatomic, and pathological features of San Francisco family A and to map the mutation responsible for disease in this family. Design: A systematic clinical, neuropsychologic, neuroimaging, and chromosome segregation analysis of San Francisco family A was performed. A pathological and biochemical assessment of a family member was made. Setting: Family study. Patients: San Francisco family A, with FTD, variable extrapyramidal symptoms, and prominent motor neuron disease. Afflicted family members donot have a MAPτ coding or splice regulatory sequence mutation, and the MAPτ is genetically excluded. Main Outcome Measures: Comparison of clinical, neuropsychologic, neuroimaging, and linkage findings of San Francisco family A with other familial forms of FTD and amyotrophic lateral sclerosis (ALS). Results: The most probable location for the mutation responsible for this condition is on chromosome arm 17q, distal to the MAPτ. All previously identified susceptibility loci for FTD and ALS are excluded. Autopsy findings from an afflicted family member show distinctive tau and α-synuclein inclusions. Another unique feature is that the insoluble tau protein consists predominantly of the 4R/0N isoform. Conclusion: The condition affecting members of San Francisco family A is clinically, pathologically, and genetically distinct from previous familial forms of FTD and ALS.
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U2 - 10.1001/archneur.61.3.398
DO - 10.1001/archneur.61.3.398
M3 - Article
C2 - 15023818
AN - SCOPUS:12144288280
SN - 0003-9942
VL - 61
SP - 398
EP - 406
JO - Archives of Neurology
JF - Archives of Neurology
IS - 3
ER -