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 Erik 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 Erik Nielsen
, Zbigniew K Wszolek
, Matthew Farrer
, Håkan Widner
, Danielle van Westen
, Douglas Hägerström
, Katerina Markopoulou
, Bruce A Chase
, Karin Nilsson
, Jan Reimer
, Christer Nilsson

Research output: Contribution to journal › Journal article › Research › peer-review

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	5
ISSN	1353-8020
DOIs	https://doi.org/10.1016/j.parkreldis.2009.06.007
Publication status	Published - 2009

Bibliographical note

Keywords: Adult; Cerebral Cortex; Female; Humans; Intermediate Filament Proteins; Male; Mutation; Parkinson Disease; Pedigree; Polymerase Chain Reaction; Sweden

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10.1016/j.parkreldis.2009.06.007

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Cite this

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.",

author = "Andreas Puschmann and Ross, \{Owen A\} and Carles Vilari{\~n}o-G{\"u}ell and Lincoln, \{Sarah J\} and Kachergus, \{Jennifer M\} and Cobb, \{Stephanie A\} and Lindquist, \{Suzanne G\} and Nielsen, \{J{\o}rgen Erik\} and Wszolek, \{Zbigniew K\} and Matthew Farrer and H{\aa}kan Widner and \{van Westen\}, Danielle and Douglas H{\"a}gerstr{\"o}m and Katerina Markopoulou and Chase, \{Bruce A\} and Karin Nilsson and Jan Reimer and Christer Nilsson",

note = "Keywords: Adult; Cerebral Cortex; Female; Humans; Intermediate Filament Proteins; Male; Mutation; Parkinson Disease; Pedigree; Polymerase Chain Reaction; Sweden",

year = "2009",

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

language = "English",

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T1 - A Swedish family with de novo alpha-synuclein A53T mutation: 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 Erik

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 - Keywords: Adult; Cerebral Cortex; Female; Humans; Intermediate Filament Proteins; Male; Mutation; Parkinson Disease; Pedigree; Polymerase Chain Reaction; Sweden

PY - 2009

Y1 - 2009

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.

U2 - 10.1016/j.parkreldis.2009.06.007

DO - 10.1016/j.parkreldis.2009.06.007

M3 - Journal article

C2 - 19632874

SN - 1353-8020

VL - 15

SP - 627

EP - 632

JO - Parkinsonism & Related Disorders

JF - Parkinsonism & Related Disorders

IS - 9

ER -