Distribution, type and origin of Parkin mutations: Review and case studies

Katja Hedrich, Cordula Eskelson, Beth Wilmot, Karen Marder, Juliette Harris, Jennifer Garrels, Helen Meija-Santana, Peter Vieregge, Helfried Jacobs, Susan B. Bressman, Anthony E. Lang, Martin Kann, Giovanni Abbruzzese, Paolo Martinelli, Eberhard Schwinger, Laurie J. Ozelius, Peter P. Pramstaller, Christine Klein, Patricia Kramer

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Early-onset Parkinson's disease (PD) has been associated with different mutations in the Parkin gene (PARK2). To study distribution and type of Parkin mutations, we carried out a comprehensive literature review that demonstrated two prominent types of mutations among 359 unrelated mutation carriers: exon rearrangements involving exon 3, 4, or both, and alterations in exons 2 and 7, suggesting mutational hot spots a founders. To elucidate the origin of 14 recurrent Parkin mutations in our samples, we carried out a detailed haplotype analysis at the PARK2 locus. Thirty-eight mutation-positive individuals, available family members, and 62 mutation-negative individuals were genotyped. We determined allele frequencies and linkage disequilibrium (LD) to evaluate the significance of shared haplotypes. We observed no LD between markers at PARK2. Our data support a common for the most frequent Parkin point mutation (924C>T; exon 7) and indicate a mutational hot spot as cause of a common small deletion (255/256delA; exon 2). Furthermore, the most frequent Parkin exon deletion (Ex4del) arose independently in 2 of our subjects. However, it also occurred as the result of a founder mutation in 2 cases that shared identical deletion break points. This study provides evidence for both mutational hot spots and founder mutations as a source of recurrent mutation in Parkin, regardless of the mutation type.

Original languageEnglish (US)
Pages (from-to)1146-1157
Number of pages12
JournalMovement Disorders
Volume19
Issue number10
DOIs
StatePublished - Oct 2004

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Mutation
Exons
Linkage Disequilibrium
Haplotypes
Point Mutation
Gene Frequency
Parkinson Disease
Genes

Keywords

  • Break point analysis
  • Distribution
  • Linkage disequilibrium
  • Origin
  • Parkin
  • Recurrent mutations

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Hedrich, K., Eskelson, C., Wilmot, B., Marder, K., Harris, J., Garrels, J., ... Kramer, P. (2004). Distribution, type and origin of Parkin mutations: Review and case studies. Movement Disorders, 19(10), 1146-1157. https://doi.org/10.1002/mds.20234

Distribution, type and origin of Parkin mutations : Review and case studies. / Hedrich, Katja; Eskelson, Cordula; Wilmot, Beth; Marder, Karen; Harris, Juliette; Garrels, Jennifer; Meija-Santana, Helen; Vieregge, Peter; Jacobs, Helfried; Bressman, Susan B.; Lang, Anthony E.; Kann, Martin; Abbruzzese, Giovanni; Martinelli, Paolo; Schwinger, Eberhard; Ozelius, Laurie J.; Pramstaller, Peter P.; Klein, Christine; Kramer, Patricia.

In: Movement Disorders, Vol. 19, No. 10, 10.2004, p. 1146-1157.

Research output: Contribution to journalArticle

Hedrich, K, Eskelson, C, Wilmot, B, Marder, K, Harris, J, Garrels, J, Meija-Santana, H, Vieregge, P, Jacobs, H, Bressman, SB, Lang, AE, Kann, M, Abbruzzese, G, Martinelli, P, Schwinger, E, Ozelius, LJ, Pramstaller, PP, Klein, C & Kramer, P 2004, 'Distribution, type and origin of Parkin mutations: Review and case studies', Movement Disorders, vol. 19, no. 10, pp. 1146-1157. https://doi.org/10.1002/mds.20234
Hedrich K, Eskelson C, Wilmot B, Marder K, Harris J, Garrels J et al. Distribution, type and origin of Parkin mutations: Review and case studies. Movement Disorders. 2004 Oct;19(10):1146-1157. https://doi.org/10.1002/mds.20234
Hedrich, Katja ; Eskelson, Cordula ; Wilmot, Beth ; Marder, Karen ; Harris, Juliette ; Garrels, Jennifer ; Meija-Santana, Helen ; Vieregge, Peter ; Jacobs, Helfried ; Bressman, Susan B. ; Lang, Anthony E. ; Kann, Martin ; Abbruzzese, Giovanni ; Martinelli, Paolo ; Schwinger, Eberhard ; Ozelius, Laurie J. ; Pramstaller, Peter P. ; Klein, Christine ; Kramer, Patricia. / Distribution, type and origin of Parkin mutations : Review and case studies. In: Movement Disorders. 2004 ; Vol. 19, No. 10. pp. 1146-1157.
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