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 alpha-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.
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 alpha-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.
Authors: Walter Struhal; Stefan Presslauer; Sabine Spielberger; Alexander Zimprich; Eduard Auff; Thomas Bruecke; Werner Poewe; Gerhard Ransmayr Journal: J Neural Transm (Vienna) Date: 2014-02-21 Impact factor: 3.575
Authors: Thierry Vilboux; Atar Lev; May Christine V Malicdan; Amos J Simon; Päivi Järvinen; Tomas Racek; Jacek Puchalka; Raman Sood; Blake Carrington; Kevin Bishop; James Mullikin; Marjan Huizing; Ben Zion Garty; Eran Eyal; Baruch Wolach; Ronit Gavrieli; Amos Toren; Michalle Soudack; Osama M Atawneh; Tatiana Babushkin; Ginette Schiby; Andrew Cullinane; Camila Avivi; Sylvie Polak-Charcon; Iris Barshack; Ninette Amariglio; Gideon Rechavi; Jutte van der Werff ten Bosch; Yair Anikster; Christoph Klein; William A Gahl; Raz Somech Journal: N Engl J Med Date: 2013-06-05 Impact factor: 91.245
Authors: Carles Vilariño-Güell; Christian Wider; Owen A Ross; Justus C Dachsel; Jennifer M Kachergus; Sarah J Lincoln; Alexandra I Soto-Ortolaza; Stephanie A Cobb; Greggory J Wilhoite; Justin A Bacon; Bahareh Behrouz; Heather L Melrose; Emna Hentati; Andreas Puschmann; Daniel M Evans; Elizabeth Conibear; Wyeth W Wasserman; Jan O Aasly; Pierre R Burkhard; Ruth Djaldetti; Joseph Ghika; Faycal Hentati; Anna Krygowska-Wajs; Tim Lynch; Eldad Melamed; Alex Rajput; Ali H Rajput; Alessandra Solida; Ruey-Meei Wu; Ryan J Uitti; Zbigniew K Wszolek; François Vingerhoets; Matthew J Farrer Journal: Am J Hum Genet Date: 2011-07-15 Impact factor: 11.025