Abstract | BACKGROUND: 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 do not have a MAP tau coding or splice regulatory sequence mutation, and the MAP tau 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 MAP tau. All previously identified susceptibility loci for FTD and ALS are excluded. Autopsy findings from an afflicted family member show distinctive tau and alpha-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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Authors | Kirk C Wilhelmsen, Mark S Forman, Howard J Rosen, Loren I Alving, Jill Goldman, Jennie Feiger, James V Lee, Samantha K Segall, Joel H Kramer, Catherine Lomen-Hoerth, Katherine P Rankin, Julene Johnson, Heidi S Feiler, Michael W Weiner, Virginia M-Y Lee, John Q Trojanowski, Bruce L Miller |
Journal | Archives of neurology
(Arch Neurol)
Vol. 61
Issue 3
Pg. 398-406
(Mar 2004)
ISSN: 0003-9942 [Print] United States |
PMID | 15023818
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Nerve Tissue Proteins
- Protein Isoforms
- SNCA protein, human
- Synucleins
- alpha-Synuclein
- tau Proteins
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Topics |
- Adult
- Aged
- Amyotrophic Lateral Sclerosis
(genetics, metabolism, pathology)
- Blotting, Western
(methods)
- Brain
(metabolism, pathology)
- Chromosomes, Human, Pair 17
- Dementia
(genetics, metabolism, pathology)
- Family Health
- Female
- Genetic Linkage
- Humans
- Inclusion Bodies
(metabolism)
- Lod Score
- Magnetic Resonance Imaging
(methods)
- Male
- Middle Aged
- Mutation
- Nerve Tissue Proteins
(metabolism)
- Neurologic Examination
(methods)
- Neuropsychological Tests
- Polymerase Chain Reaction
(methods)
- Protein Isoforms
(metabolism)
- Synucleins
- alpha-Synuclein
- tau Proteins
(genetics, metabolism)
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