TY - JOUR
T1 - A Swedish family with de novo α-synuclein A53T mutation
T2 - Evidence for early cortical dysfunction
AU - Puschmann, Andreas
AU - Ross, Owen A.
AU - Vilariño-Güell, Carles
AU - Lincoln, Sarah J.
AU - Kachergus, Jennifer M.
AU - Cobb, Stephanie A.
AU - Lindquist, Suzanne G.
AU - Nielsen, Jørgen E.
AU - Wszolek, Zbigniew K.
AU - Farrer, Matthew
AU - Widner, Håkan
AU - van Westen, Danielle
AU - Hägerström, Douglas
AU - Markopoulou, Katerina
AU - Chase, Bruce A.
AU - Nilsson, Karin
AU - Reimer, Jan
AU - Nilsson, Christer
N1 - Funding Information:
Andreas Puschmann, Håkan Widner, Karin Nilsson, Jan Reimer, and Christer Nilsson received funding from The Swedish Parkinson Academy, The Research Foundation of the Swedish Parkinson's Disease Association, Lund University Research Fund, and The Royal Physiographic Society in Lund. Owen A. Ross, Carles Vilariño-Güell, Sarah J. Lincoln, Jennifer M. Kachergus, Stephanie A. Cobb, Zbigniew K. Wszolek, Matthew J. Farrer are supported by NIH/NINDS Morris K. Udall Center for Excellence in PD Research at Mayo Clinic (P50 NS40256) grant, NIH/NIA (P01AG017216) grant, and Pacific Research Alzheimer's Foundation (PARF C06-01) grant. Zbigniew K. Wszolek is also supported by NIH/NIA R01AG015866 grant. Bruce A. Chase received funding from NIH NINDS R15 NS043162. Suzanne G. Lindquist, Jørgen E. Nielsen, Danielle van Westen, Douglas Hägerström, and Katerina Markopoulou: No disclosures.
PY - 2009/11/5
Y1 - 2009/11/5
N2 - A de novo α-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.
AB - A de novo α-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.
KW - A53T
KW - A53T mutation
KW - Ala53Thr
KW - Alpha-synuclein
KW - Autosomal dominant parkinsonism
KW - Biomarkers
KW - CSF examination
KW - Cerebrospinal fluid
KW - Electroencephalogram
KW - Haplotype analysis
KW - Longitudinal clinical follow-up
KW - Magnetic resonance imaging
KW - Myoclonus
KW - Neuroimaging
KW - Parkinson disease
KW - Parkinsonian conditions
KW - SPECT
KW - Single-photon emission computed tomography
UR - http://www.scopus.com/inward/record.url?scp=70350149351&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350149351&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2009.06.007
DO - 10.1016/j.parkreldis.2009.06.007
M3 - Article
C2 - 19632874
AN - SCOPUS:70350149351
SN - 1353-8020
VL - 15
SP - 627
EP - 632
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 9
ER -