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Detection of Parkin ( PARK2 ) and DJ1 ( PARK7 ) mutations in early‐onset Parkinson disease: Parkin mutation frequency depends on ethnic origin of patients
Author(s) -
Djarmati Ana,
Hedrich Katja,
Svetel Marina,
Schäfer Nora,
Juric Vladislava,
Vukosavic Slobodanka,
Hering Robert,
Riess Olaf,
Romac Stanka,
Klein Christine,
Kostic Vladimir
Publication year - 2004
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9240
Subject(s) - exon , parkin , genetics , biology , mutation , point mutation , compound heterozygosity , mutation frequency , microbiology and biotechnology , gene , parkinson's disease , disease , pathology , medicine
Mutations in the Parkin ( PARK2 ) and the DJ1 ( PARK7 ) gene cause early‐onset Parkinson disease (EOPD). We tested 75 Serbian EOPD patients for mutations in both genes by conventional mutational screening (SSCP/dHPLC/sequencing) to detect small sequence alterations and by gene dosage studies (quantitative PCR) to reveal deletions or multiplications of one or more exons. A compound heterozygous Parkin mutation (exon deletion and point mutation; [c.836_972del]+[c.1411C>T]; +1 is first nucleotide of GenBank AB009973.1) was identified in a patient who showed a relatively benign course after a disease onset at 41 years. Another case had a heterozygous exon deletion in DJ1 ([c.253_322del]+[?]) and presented with an age at onset of 45 years and a rapid disease course. In conclusion, Parkin mutations are surprisingly rare in our Serbian EOPD sample, suggesting that the mutation rate depends on the ethnic origin of the patients. Although DJ1 mutations appear to be rare, we confirm their role in EOPD and demonstrate the importance of gene dosage studies. © 2004 Wiley‐Liss, Inc.