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

*Corresponding author for this work
158 Citations (Scopus)


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
JournalMovement Disorders
Issue number10
Pages (from-to)1146-1157
Number of pages12
Publication statusPublished - 01.10.2004


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