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Distribution, type, and origin of Parkin mutations: Review and case studies
Author(s) -
Hedrich Katja,
Eskelson Cordula,
Wilmot Beth,
Marder Karen,
Harris Juliette,
Garrels Jennifer,
MeijaSantana 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
Publication year - 2004
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.20234
Subject(s) - parkin , genetics , exon , biology , haplotype , point mutation , mutation , locus (genetics) , linkage disequilibrium , allele , gene , parkinson's disease , disease , medicine , pathology
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 379 unrelated mutation carriers: exon rearrangements involving exon 3, 4, or both, and alterations in exons 2 and 7, suggesting mutational hot spots or 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 founder 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 mutations in Parkin , regardless of the mutation type. © 2004 Movement Disorder Society