1. A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction.
- Author
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Puschmann A, Ross OA, Vilariño-Güell C, Lincoln SJ, Kachergus JM, Cobb SA, Lindquist SG, Nielsen JE, Wszolek ZK, Farrer M, Widner H, van Westen D, Hägerström D, Markopoulou K, Chase BA, Nilsson K, Reimer J, Nilsson C, Puschmann, Andreas, and Ross, Owen A
- Subjects
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GREEK Americans , *GENETIC mutation , *CYTOSKELETAL proteins , *PARKINSON'S disease , *RESEARCH funding , *GENETIC techniques , *POLYMERASE chain reaction , *CEREBRAL cortex , *GENEALOGY - Abstract
A de novo alpha-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. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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