A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction

Andreas Puschmann; Owen A Ross; Carles Vilariño-Güell; Sarah J Lincoln; Jennifer M Kachergus; Stephanie A Cobb; Suzanne G Lindquist; Jørgen E Nielsen; Zbigniew K Wszolek; Matthew Farrer; Håkan Widner; Danielle van Westen; Douglas Hägerström; Katerina Markopoulou; Bruce A Chase; Karin Nilsson; Jan Reimer; Christer Nilsson

doi:10.1016/j.parkreldis.2009.06.007

A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction

Andreas Puschmann, Owen A Ross, Carles Vilariño-Güell, Sarah J Lincoln, Jennifer M Kachergus, Stephanie A Cobb, Suzanne G Lindquist, Jørgen E Nielsen, Zbigniew K Wszolek, Matthew Farrer, Håkan Widner, Danielle van Westen, Douglas Hägerström, Katerina Markopoulou, Bruce A Chase, Karin Nilsson, Jan Reimer, Christer Nilsson

97 Citations (Scopus)

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.

Original language	English
Journal	Parkinsonism & related disorders
Volume	15
Issue number	9
Pages (from-to)	627-32
Number of pages	6
ISSN	1353-8020
DOIs	https://doi.org/10.1016/j.parkreldis.2009.06.007
Publication status	Published - Nov 2009
Externally published	Yes

Keywords

Adult
Cerebral Cortex/pathology
Female
Humans
Intermediate Filament Proteins/genetics
Male
Mutation
Parkinson Disease/genetics
Pedigree
Polymerase Chain Reaction
Sweden

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10.1016/j.parkreldis.2009.06.007

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Puschmann, A., Ross, O. A., Vilariño-Güell, C., Lincoln, S. J., Kachergus, J. M., Cobb, S. A., Lindquist, S. G., Nielsen, J. E., Wszolek, Z. K., Farrer, M., Widner, H., van Westen, D., Hägerström, D., Markopoulou, K., Chase, B. A., Nilsson, K., Reimer, J., & Nilsson, C. (2009). A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction. Parkinsonism & related disorders, 15(9), 627-32. https://doi.org/10.1016/j.parkreldis.2009.06.007

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 2009, 'A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction', Parkinsonism & related disorders, vol. 15, no. 9, pp. 627-32. https://doi.org/10.1016/j.parkreldis.2009.06.007

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title = "A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction",

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.",

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doi = "10.1016/j.parkreldis.2009.06.007",

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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

PY - 2009/11

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N2 - 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.

AB - 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.

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KW - Cerebral Cortex/pathology

KW - Female

KW - Humans

KW - Intermediate Filament Proteins/genetics

KW - Male

KW - Mutation

KW - Parkinson Disease/genetics

KW - Pedigree

KW - Polymerase Chain Reaction

KW - Sweden

UR - https://www.scopus.com/pages/publications/70350149351

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SP - 627

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JO - Parkinsonism & related disorders

JF - Parkinsonism & related disorders

IS - 9

ER -

A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction

Abstract

Keywords

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