Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers - PubMed (original) (raw)
Comparative Study
doi: 10.1002/ana.20587.
Michael G Schlossmacher, Thomas S Jacques, Francesco Scaravilli, Cordula Eskelson, Imelda Pepivani, Katja Hedrich, Susanna Adel, Melissa Gonzales-McNeal, Rüdiger Hilker, Patricia L Kramer, Christine Klein
Affiliations
- PMID: 16130111
- DOI: 10.1002/ana.20587
Comparative Study
Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers
Peter P Pramstaller et al. Ann Neurol. 2005 Sep.
Abstract
We report the clinical, genetic, and neuropathological findings of a seven generation-spanning pedigree with 196 individuals, 25 of whom had levodopa-responsive parkinsonism. Genetic analyses indicated Parkin mutations in 77 subjects. Among the 25 patients, 5 carried compound heterozygous mutations and met criteria for definite Parkinson's disease (PD) according to UK PD Society Brain Bank guidelines; 8 subjects carried only a heterozygous Parkin mutation. The mutational status of five deceased patients was unknown, and seven PD patients had no Parkin mutation. Survival analyses showed a significant difference in the age-at-onset distribution between patients with compound heterozygous mutations and the groups of heterozygous carriers and subjects without detectable Parkin mutations. Autopsy of a 73-year-old patient, who carried two mutant Parkin alleles (delExon7 + del1072T), showed PD-type cell loss, reactive gliosis, and alpha-synuclein-positive Lewy bodies in the substantia nigra and locus ceruleus. Surviving neurons were reactive with antibodies to the N terminus of Parkin but not the In-Between-RING ("IBR") domain, which had been deleted by both mutations. This large Parkin pedigree represents a unique opportunity to prospectively study the role of heterozygous Parkin mutations as a PD risk factor, to identify additional contributors to the expression of late-onset PD in heterozygous carriers, and to reexamine the role of Parkin in inclusion formation.
Similar articles
- Early-onset Parkinson's disease caused by a novel parkin mutation in a genetic isolate from north-eastern Brazil.
Chien HF, Rohé CF, Costa MD, Breedveld GJ, Oostra BA, Barbosa ER, Bonifati V. Chien HF, et al. Neurogenetics. 2006 Mar;7(1):13-9. doi: 10.1007/s10048-005-0017-x. Epub 2005 Nov 22. Neurogenetics. 2006. PMID: 16328510 - Lewy bodies and parkinsonism in families with parkin mutations.
Farrer M, Chan P, Chen R, Tan L, Lincoln S, Hernandez D, Forno L, Gwinn-Hardy K, Petrucelli L, Hussey J, Singleton A, Tanner C, Hardy J, Langston JW. Farrer M, et al. Ann Neurol. 2001 Sep;50(3):293-300. doi: 10.1002/ana.1132. Ann Neurol. 2001. PMID: 11558785 - Parkinson's disease with Lewy bodies associated with a heterozygous PARKIN dosage mutation.
Sharp ME, Marder KS, Côté L, Clark LN, Nichols WC, Vonsattel JP, Alcalay RN. Sharp ME, et al. Mov Disord. 2014 Apr;29(4):566-8. doi: 10.1002/mds.25792. Epub 2013 Dec 27. Mov Disord. 2014. PMID: 24375549 Free PMC article. - [Etiology and pathogenesis of Parkinson's disease: from mitochondrial dysfunctions to familial Parkinson's disease].
Hattori N. Hattori N. Rinsho Shinkeigaku. 2004 Apr-May;44(4-5):241-62. Rinsho Shinkeigaku. 2004. PMID: 15287506 Review. Japanese. - Distribution, type, and origin of Parkin mutations: review and case studies.
Hedrich K, Eskelson C, Wilmot B, Marder K, Harris J, Garrels J, Meija-Santana H, Vieregge P, Jacobs H, Bressman SB, Lang AE, Kann M, Abbruzzese G, Martinelli P, Schwinger E, Ozelius LJ, Pramstaller PP, Klein C, Kramer P. Hedrich K, et al. Mov Disord. 2004 Oct;19(10):1146-57. doi: 10.1002/mds.20234. Mov Disord. 2004. PMID: 15390068 Review.
Cited by
- Deficiency of parkin causes neurodegeneration and accumulation of pathological α-synuclein in monkey models.
Han R, Wang Q, Xiong X, Chen X, Tu Z, Li B, Zhang F, Chen C, Pan M, Xu T, Chen L, Wang Z, Liu Y, He D, Guo X, He F, Wu P, Yin P, Liu Y, Yan X, Li S, Li XJ, Yang W. Han R, et al. J Clin Invest. 2024 Oct 15;134(20):e179633. doi: 10.1172/JCI179633. J Clin Invest. 2024. PMID: 39403921 Free PMC article. - α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson's disease.
Geibl FF, Henrich MT, Xie Z, Zampese E, Ueda J, Tkatch T, Wokosin DL, Nasiri E, Grotmann CA, Dawson VL, Dawson TM, Chandel NS, Oertel WH, Surmeier DJ. Geibl FF, et al. Mol Neurodegener. 2024 Oct 8;19(1):69. doi: 10.1186/s13024-024-00756-2. Mol Neurodegener. 2024. PMID: 39379975 Free PMC article. - Peripheral cutaneous synucleinopathy characteristics in genetic Parkinson's disease.
Yuan Y, Wang Y, Liu M, Luo H, Liu X, Li L, Mao C, Yang T, Li S, Zhang X, Gao Y, Xu Y, Yang J. Yuan Y, et al. Front Neurol. 2024 May 1;15:1404492. doi: 10.3389/fneur.2024.1404492. eCollection 2024. Front Neurol. 2024. PMID: 38751879 Free PMC article. - Analysis of α-syn and parkin interaction in mediating neuronal death in Drosophila model of Parkinson's disease.
Narwal S, Singh A, Tare M. Narwal S, et al. Front Cell Neurosci. 2024 Jan 4;17:1295805. doi: 10.3389/fncel.2023.1295805. eCollection 2023. Front Cell Neurosci. 2024. PMID: 38239290 Free PMC article. - Mitochondrial dysfunction in Parkinson's disease - a key disease hallmark with therapeutic potential.
Henrich MT, Oertel WH, Surmeier DJ, Geibl FF. Henrich MT, et al. Mol Neurodegener. 2023 Nov 11;18(1):83. doi: 10.1186/s13024-023-00676-7. Mol Neurodegener. 2023. PMID: 37951933 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous