These authors contributed equally to this work.
Mutations in Brief
Article first published online: 10 MAR 2008
© 2008 Wiley-Liss, Inc.
Special Issue: Focus on Pharmacogenetics
Volume 29, Issue 4, page 565, April 2008
How to Cite
Marongiu, R., Ferraris, A., Ialongo, T., Michiorri, S., Soleti, F., Ferrari, F., Elia, A. E., Ghezzi, D., Albanese, A., Altavista, M. C., Antonini, A., Barone, P., Brusa, L., Cortelli, P., Martinelli, P., Pellecchia, M. T., Pezzoli, G., Scaglione, C., Stanzione, P., Tinazzi, M., Zecchinelli, A., Zeviani, M., Cassetta, E., Garavaglia, B., Dallapiccola, B., Bentivoglio, A. R. and Valente, E. M. (2008), PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum. Hum. Mutat., 29: 565. doi: 10.1002/humu.20719
Communicated by Mark H. Paalman
Online Citation: Human Mutation, Mutation in Brief #1000(2008) Onlinehttp://www3.interscience.wiley.com/homepages/38515/1000.pdf
Additional members listed in the acknowledgments.
- Issue published online: 10 MAR 2008
- Article first published online: 10 MAR 2008
- Manuscript Accepted: 3 DEC 2007
- Manuscript Received: 7 SEP 2007
- Italian Telethon Foundation, Italian Ministry of Health, MIUR. Grant Number: Telethon grant n. GGP04291 to EMV and grant n. GTF04007 to GP; Ricerca Corrente 2006 and Ricerca Finalizzata 2004 and 2006 to BD, Ricerca Scientifica Facoltà 2006 to BD, Ricerca Scientifica FIRB2003 to MZ
- Cited By
- Parkinson disease;
- autosomal recessive parkinsonism;
- heterozygous rare variants
Heterozygous rare variants in the PINK1 gene, as well as in other genes causing autosomal recessive parkinsonism, have been reported both in patients and healthy controls. Their pathogenic significance is uncertain, but they have been suggested to represent risk factors to develop Parkinson disease (PD). The few large studies that assessed the frequency of PINK1 heterozygotes in cases and controls yielded controversial results, and the phenotypic spectrum is largely unknown. We retrospectively analyzed the occurrence of PINK1 heterozygous rare variants in over 1100 sporadic and familial patients of all onset ages and in 400 controls. Twenty patients and 6 controls were heterozygous, with frequencies (1.8% vs. 1.5%) not significantly different in the two groups. Clinical features of heterozygotes were indistinguishable to those of wild-type patients, with mean disease onset 10 years later than in carriers of two mutations but worse disease progression. A meta-analysis indicated that, in PINK1 heterozygotes, the PD risk is only slightly increased with a non significant odds ratio of 1.62. These findings suggest that PINK1 heterozygous rare variants play only a minor susceptibility role in the context of a multifactorial model of PD. Hence, their significance should be kept distinct from that of homozygous/compound heterozygous mutations, that cause parkinsonism inherited in a mendelian fashion. © 2008 Wiley-Liss, Inc.