TY - JOUR
T1 - Alpha-synuclein multiplications with parkinsonism, dementia or progressive myoclonus?
AU - Puschmann, Andreas
AU - Wszolek, Zbigniew K.
AU - Farrer, Matthew
AU - Gustafson, Lars
AU - Widner, Håkan
AU - Nilsson, Christer
N1 - Funding Information:
The study was supported by grants from the Swedish Parkinson Foundation and the Swedish Parkinson Academy to AP, CN and HW. ZKW and MJF are funded by the National Institute of Neurological Disorders and Stroke P50 NS40256 Udall Center grant awarded to the Mayo Clinic, Jacksonville, and by the Pacific Alzheimer Research Foundation Center grant (PARF C06-01).
PY - 2009/6
Y1 - 2009/6
N2 - Duplications and triplications of the alpha-synuclein (SNCA) gene have been reported in Parkinson's disease patients belonging to the Southern Swedish "Lister family". Further genealogical research has now shown that these individuals are descended from a large kindred characterized by Herman Lundborg in 1901-1913. In the expanded pedigree, a total of 25 individuals had Parkinson's disease with an autosomal dominant pattern of inheritance. Hereditary dementia, and, historically, dementia praecox have been described in other family members. Furthermore, an autosomal recessively inherited pediatric disease with nocturnal tonic-clonic fits, subsequent progressive myoclonus, startle reactions, tremor and muscle rigidity was described by Lundborg in the same pedigree. The entity was later designated Unverricht-Lundborg disease (ULD) or progressive myoclonus epilepsy type 1 (EPM1). However, Lundborg's clinical description of this disease, based on 17 patients within this kindred, differs from the modern definition of EPM1, which relies on patients with a mutation in the cystatin B (CSTB) gene. We hypothesize that the former pediatric disease, as well as the parkinsonism and dementia phenotypes, are associated with duplications, triplications and possibly higher-order multiplications of the alpha-synuclein (SNCA) gene. This hypothesis is supported by the distribution of afflicted family members within the pedigree and by recently obtained genealogical information.
AB - Duplications and triplications of the alpha-synuclein (SNCA) gene have been reported in Parkinson's disease patients belonging to the Southern Swedish "Lister family". Further genealogical research has now shown that these individuals are descended from a large kindred characterized by Herman Lundborg in 1901-1913. In the expanded pedigree, a total of 25 individuals had Parkinson's disease with an autosomal dominant pattern of inheritance. Hereditary dementia, and, historically, dementia praecox have been described in other family members. Furthermore, an autosomal recessively inherited pediatric disease with nocturnal tonic-clonic fits, subsequent progressive myoclonus, startle reactions, tremor and muscle rigidity was described by Lundborg in the same pedigree. The entity was later designated Unverricht-Lundborg disease (ULD) or progressive myoclonus epilepsy type 1 (EPM1). However, Lundborg's clinical description of this disease, based on 17 patients within this kindred, differs from the modern definition of EPM1, which relies on patients with a mutation in the cystatin B (CSTB) gene. We hypothesize that the former pediatric disease, as well as the parkinsonism and dementia phenotypes, are associated with duplications, triplications and possibly higher-order multiplications of the alpha-synuclein (SNCA) gene. This hypothesis is supported by the distribution of afflicted family members within the pedigree and by recently obtained genealogical information.
KW - Alpha-synuclein
KW - Dementia
KW - EPM1
KW - Gene multiplication
KW - Hyperekplexia
KW - Myoclonus
KW - Parkinson's disease
KW - Progressive myoclonic epilepsy
KW - Startle reaction
KW - Unverricht-Lundborg disease
UR - http://www.scopus.com/inward/record.url?scp=67349253834&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349253834&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2008.08.002
DO - 10.1016/j.parkreldis.2008.08.002
M3 - Article
C2 - 18824390
AN - SCOPUS:67349253834
SN - 1353-8020
VL - 15
SP - 390
EP - 392
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 5
ER -