TY - JOUR
T1 - Autosomal dominant dopa-responsive parkinsonism in a multigenerational Swiss family
AU - Wider, C.
AU - Skipper, L.
AU - Solida, A.
AU - Brown, L.
AU - Farrer, M.
AU - Dickson, D.
AU - Wszolek, Z. K.
AU - Vingerhoets, F. J.G.
N1 - Funding Information:
We are grateful to the patients and their families for their collaboration. C.W. received support from the Swiss National Science Foundation, the Swiss Parkinson's disease Foundation, and the Robert and Clarice Smith Fellowhip program. M.F., D.D. and Z.K.W. are supported by the Morris K. Udall NIH/NINDS Parkinson disease Center of Excellence Grant awarded to the Mayo Clinic Jacksonville (P01 NS0256). Many thanks to Sarah Lincoln, Jennifer Kachergus and Mary Hulihan for their technical support.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/8
Y1 - 2008/8
N2 - Aim: To describe a large family with autosomal dominant parkinsonism. Background: Seven genes are directly implicated in autosomally inherited parkinsonism. However, there are several multigenerational large families known with no identifiable mutation. Material and methods: Family members were evaluated clinically, by history and chart review. Genetic investigation included SCA2, SCA3, UCHL1, SNCA, LRRK2, PINK1, PRKN, PGRN, FMR1 premutation, and MAPT. The proband underwent brain fluorodopa PET (FD-PET) scan, and one autopsy was available. Results: Eleven patients had a diagnosis of Parkinson's disease (PD), nine women. Mean age of onset was 52 with tremor-predominant dopa-responsive parkinsonism. Disease progression was slow but severe motor fluctuations occurred. One patient required subthalamic nucleus deep-brain stimulation with a good motor outcome. One patient had mental retardation, schizophrenia and became demented, and another patient was demented. Three patients and also two unaffected subjects had mild learning difficulties. All genetic tests yielded negative results. FD-PET showed marked asymmetric striatal tracer uptake deficiency, consistent with PD. Pathological examination demonstrated no Lewy bodies and immunostaining was negative for α-synuclein. Conclusion: Apart from a younger age of onset and a female predominance, the phenotype was indistinguishable from sporadic tremor-predominant PD, including FD-PET scan results. As known genetic causes of autosomal dominant PD were excluded, this family harbors a novel genetic defect.
AB - Aim: To describe a large family with autosomal dominant parkinsonism. Background: Seven genes are directly implicated in autosomally inherited parkinsonism. However, there are several multigenerational large families known with no identifiable mutation. Material and methods: Family members were evaluated clinically, by history and chart review. Genetic investigation included SCA2, SCA3, UCHL1, SNCA, LRRK2, PINK1, PRKN, PGRN, FMR1 premutation, and MAPT. The proband underwent brain fluorodopa PET (FD-PET) scan, and one autopsy was available. Results: Eleven patients had a diagnosis of Parkinson's disease (PD), nine women. Mean age of onset was 52 with tremor-predominant dopa-responsive parkinsonism. Disease progression was slow but severe motor fluctuations occurred. One patient required subthalamic nucleus deep-brain stimulation with a good motor outcome. One patient had mental retardation, schizophrenia and became demented, and another patient was demented. Three patients and also two unaffected subjects had mild learning difficulties. All genetic tests yielded negative results. FD-PET showed marked asymmetric striatal tracer uptake deficiency, consistent with PD. Pathological examination demonstrated no Lewy bodies and immunostaining was negative for α-synuclein. Conclusion: Apart from a younger age of onset and a female predominance, the phenotype was indistinguishable from sporadic tremor-predominant PD, including FD-PET scan results. As known genetic causes of autosomal dominant PD were excluded, this family harbors a novel genetic defect.
KW - Autosomal dominant
KW - Familial
KW - Parkinson's disease
KW - Parkinsonism
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U2 - 10.1016/j.parkreldis.2007.11.013
DO - 10.1016/j.parkreldis.2007.11.013
M3 - Article
C2 - 18342564
AN - SCOPUS:49649103203
SN - 1353-8020
VL - 14
SP - 465
EP - 470
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 6
ER -