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Novel parkin mutations detected in patients with early‐onset Parkinson's disease
Author(s) -
BertoliAvella Aida M.,
GiroudBenitez José L.,
Akyol Ali,
Barbosa Egberto,
Schaap Onno,
van der Linde Herma C.,
Martigi Emilia,
Lopiano Leonardo,
Lamberti Paolo,
Fincati Emiliana,
Antonini Angelo,
Stocchi Fabrizio,
Montagna Pasquale,
Squitieri Ferdinando,
Marini Paolo,
Abbruzzese Giovanni,
Fabbrini Giovanni,
Marconi Roberto,
Dalla Libera Alessio,
Trianni Giorgio,
Guidi Marco,
De Gaetano Antonio,
Boff Maegawa Gustavo,
De Leo Antonino,
Gallai Virgilio,
de Rosa Giulia,
Vanacore Nicola,
Meco Giuseppe,
van Duijn Cornelia M.,
Oostra Ben A.,
Heutink Peter,
Bonifati Vincenzo
Publication year - 2005
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.20343
Subject(s) - parkin , parkinson's disease , medicine , degenerative disease , disease , age of onset , central nervous system disease , clinical neurology , pediatrics , psychology , neuroscience
A multiethnic series of patients with early‐onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin /PARK2 gene mutations and to investigate phenotype–genotype relationships. Forty‐six EOP probands with an onset age of <45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost‐effective, real‐time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11‐3C>G, and exon 8‐9‐10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work‐up of EOP. © 2004 Movement Disorder Society