Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication.

Research output: Contribution to journalArticle


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.


  • J Fuchs
  • Christer Nilsson
  • J Kachergus
  • M Munz
  • Elna-Marie Larsson
  • B Schule
  • J W Langston
  • F A Middleton
  • O A Ross
  • M Hulihan
  • T Gasser
  • M J Farrer
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
Original languageEnglish
Pages (from-to)916-922
Issue number12
Publication statusPublished - 2007
Publication categoryResearch

Bibliographic note

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)