Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication.
(2007) In Neurology 68(12). p.916-922- Abstract
- Background: The " Lister family complex," an extensive Swedish family with autosomal dominant Parkinson disease, was first described by Henry Mjones in 1949. On the basis of clinical, molecular, and genealogic findings on a Swedish and an American family branch, we provide genetic evidence that explains the parkinsonism in this extended pedigree. Methods: Clinical methods included a detailed neurologic exam of the proband of the Swedish family branch, MRI, and ([ 123] I) - beta - CIT SPECT imaging. Genomic analysis included alpha-synuclein sequencing, SNCA real-time PCR dosage, chromosome 4q21 microsatellite analysis, and high-resolution microarray genotyping. The geographic origin and ancestral genealogy of each pedigree were researched... (More)
- Background: The " Lister family complex," an extensive Swedish family with autosomal dominant Parkinson disease, was first described by Henry Mjones in 1949. On the basis of clinical, molecular, and genealogic findings on a Swedish and an American family branch, we provide genetic evidence that explains the parkinsonism in this extended pedigree. Methods: Clinical methods included a detailed neurologic exam of the proband of the Swedish family branch, MRI, and ([ 123] I) - beta - CIT SPECT imaging. Genomic analysis included alpha-synuclein sequencing, SNCA real-time PCR dosage, chromosome 4q21 microsatellite analysis, and high-resolution microarray genotyping. The geographic origin and ancestral genealogy of each pedigree were researched in the medical literature and Swedish Parish records. Results: The proband of the Swedish family branch presented with early dysautonomia followed by progressive parkinsonism suggestive of multiple system atrophy. Molecular analysis identified a genomic duplication of < 0.9 Mb encompassing alpha-synuclein and multimerin 1 ( SNCA- MMRN1), flanked by long interspersed repeat sequences ( LINE L1). Microsatellite variability within the genomic interval was identical to that previously described for a Swedish American family with an alpha- synuclein triplication. Subsequent genealogic investigation suggested that both kindreds are ancestrally related to the Lister family complex. Conclusion: Our findings extend clinical, genetic, and genealogical research on the Lister family complex. The genetic basis for familial parkinsonism is an SNCA- MMRN11 multiplication, but whereas SNCA- MMRN1 duplication in the Swedish proband ( Branch J) leads to late- onset autonomic dysfunction and parkinsonism, SNCA- MMRN1 triplication in the Swedish American family ( Branch I) leads to early- onset Parkinson disease and dementia. (Less)
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https://lup.lub.lu.se/record/164655
- author
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Neurology
- volume
- 68
- issue
- 12
- pages
- 916 - 922
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000245034400009
- scopus:34147109175
- pmid:17251522
- ISSN
- 1526-632X
- DOI
- 10.1212/01.wnl.0000254458.17630.c5
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Psychogeriatrics (013304000), Diagnostic Radiology, (Lund) (013038000)
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- fef0bfeb-5c01-4470-ad57-003c8a07f7bb (old id 164655)
- date added to LUP
- 2016-04-01 15:17:41
- date last changed
- 2022-04-22 06:58:46
@article{fef0bfeb-5c01-4470-ad57-003c8a07f7bb,
abstract = {{Background: The " Lister family complex," an extensive Swedish family with autosomal dominant Parkinson disease, was first described by Henry Mjones in 1949. On the basis of clinical, molecular, and genealogic findings on a Swedish and an American family branch, we provide genetic evidence that explains the parkinsonism in this extended pedigree. Methods: Clinical methods included a detailed neurologic exam of the proband of the Swedish family branch, MRI, and ([ 123] I) - beta - CIT SPECT imaging. Genomic analysis included alpha-synuclein sequencing, SNCA real-time PCR dosage, chromosome 4q21 microsatellite analysis, and high-resolution microarray genotyping. The geographic origin and ancestral genealogy of each pedigree were researched in the medical literature and Swedish Parish records. Results: The proband of the Swedish family branch presented with early dysautonomia followed by progressive parkinsonism suggestive of multiple system atrophy. Molecular analysis identified a genomic duplication of < 0.9 Mb encompassing alpha-synuclein and multimerin 1 ( SNCA- MMRN1), flanked by long interspersed repeat sequences ( LINE L1). Microsatellite variability within the genomic interval was identical to that previously described for a Swedish American family with an alpha- synuclein triplication. Subsequent genealogic investigation suggested that both kindreds are ancestrally related to the Lister family complex. Conclusion: Our findings extend clinical, genetic, and genealogical research on the Lister family complex. The genetic basis for familial parkinsonism is an SNCA- MMRN11 multiplication, but whereas SNCA- MMRN1 duplication in the Swedish proband ( Branch J) leads to late- onset autonomic dysfunction and parkinsonism, SNCA- MMRN1 triplication in the Swedish American family ( Branch I) leads to early- onset Parkinson disease and dementia.}},
author = {{Fuchs, J and Nilsson, Christer and Kachergus, J and Munz, M and Larsson, Elna-Marie and Schule, B and Langston, J W and Middleton, F A and Ross, O A and Hulihan, M and Gasser, T and Farrer, M J}},
issn = {{1526-632X}},
language = {{eng}},
number = {{12}},
pages = {{916--922}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Neurology}},
title = {{Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication.}},
url = {{http://dx.doi.org/10.1212/01.wnl.0000254458.17630.c5}},
doi = {{10.1212/01.wnl.0000254458.17630.c5}},
volume = {{68}},
year = {{2007}},
}