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

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.

Originalsprog	Engelsk
Tidsskrift	Parkinsonism & related disorders
Vol/bind	15
Udgave nummer	9
Sider (fra-til)	627-32
Antal sider	6
ISSN	1353-8020
DOI	https://doi.org/10.1016/j.parkreldis.2009.06.007
Status	Udgivet - nov. 2009
Udgivet eksternt	Ja

Adgang til dokumentet

10.1016/j.parkreldis.2009.06.007

Citationsformater

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, bind 15, nr. 9, s. 627-32. https://doi.org/10.1016/j.parkreldis.2009.06.007

@article{3cce35e4a2aa4d84bf7fa6c65df979e5,

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.",

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

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 E} 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",

year = "2009",

month = nov,

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

language = "English",

volume = "15",

pages = "627--32",

journal = "Parkinsonism & related disorders",

issn = "1353-8020",

publisher = "Elsevier Ltd",

number = "9",

}

TY - JOUR

T1 - A Swedish family with de novo alpha-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

PY - 2009/11

Y1 - 2009/11

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.

KW - Adult

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

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 -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater