Tags

Type your tag names separated by a space and hit enter

PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism.
Eur J Hum Genet. 2005 Sep; 13(9):1086-93.EJ

Abstract

Recessively inherited early-onset parkinsonism (EOP) has been associated with mutations in the Parkin, DJ-1, and PINK1 genes. We studied the prevalence of mutations in all three genes in 65 Italian patients (mean age of onset: 43.2+/-5.4 years, 62 sporadic, three familial), selected by age at onset equal or younger than 51 years. Clinical features were compatible with idiopathic Parkinson's disease in all cases. To detect small sequence alterations in Parkin, DJ-1, and PINK1, we performed a conventional mutational analysis (SSCP/dHPLC/sequencing) of all coding exons of these genes. To test for the presence of exon rearrangements in PINK1, we established a new quantitative duplex PCR assay. Gene dosage alterations in Parkin and DJ-1 were excluded using previously reported protocols. Five patients (8%; one woman/four men; mean age at onset: 38.2+/-9.7 (range 25-49) years) carried mutations in one of the genes studied: three cases had novel PINK1 mutations, one of which occurred twice (homozygous c.1602_1603insCAA; heterozygous c.1602_1603insCAA; heterozygous c.836G>A), and two patients had known Parkin mutations (heterozygous c.734A>T and c.924C>T; heterozygous c.924C>T). Family history was negative for all mutation carriers, but one with a history of tremor. Additionally, we detected one novel polymorphism (c.344A>T) and four novel PINK1 changes of unknown pathogenic significance (-21G/A; IVS1+97A/G; IVS3+38_40delTTT; c.852C>T), but no exon rearrangements. No mutations were found in the DJ-1 gene. The number of mutation carriers in both the Parkin and the PINK1 gene in our cohort is low but comparable, suggesting that PINK1 has to be considered in EOP.

Authors+Show Affiliations

Department of Neurology, University of Lübeck, Lübeck, Germany. christine.klein@neuro.uni-luebeck.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15970950

Citation

Klein, Christine, et al. "PINK1, Parkin, and DJ-1 Mutations in Italian Patients With Early-onset Parkinsonism." European Journal of Human Genetics : EJHG, vol. 13, no. 9, 2005, pp. 1086-93.
Klein C, Djarmati A, Hedrich K, et al. PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism. Eur J Hum Genet. 2005;13(9):1086-93.
Klein, C., Djarmati, A., Hedrich, K., Schäfer, N., Scaglione, C., Marchese, R., Kock, N., Schüle, B., Hiller, A., Lohnau, T., Winkler, S., Wiegers, K., Hering, R., Bauer, P., Riess, O., Abbruzzese, G., Martinelli, P., & Pramstaller, P. P. (2005). PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism. European Journal of Human Genetics : EJHG, 13(9), 1086-93.
Klein C, et al. PINK1, Parkin, and DJ-1 Mutations in Italian Patients With Early-onset Parkinsonism. Eur J Hum Genet. 2005;13(9):1086-93. PubMed PMID: 15970950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism. AU - Klein,Christine, AU - Djarmati,Ana, AU - Hedrich,Katja, AU - Schäfer,Nora, AU - Scaglione,Cesa, AU - Marchese,Roberta, AU - Kock,Norman, AU - Schüle,Birgitt, AU - Hiller,Anja, AU - Lohnau,Thora, AU - Winkler,Susen, AU - Wiegers,Karin, AU - Hering,Robert, AU - Bauer,Peter, AU - Riess,Olaf, AU - Abbruzzese,Giovanni, AU - Martinelli,Paolo, AU - Pramstaller,Peter P, PY - 2005/6/23/pubmed PY - 2005/10/28/medline PY - 2005/6/23/entrez SP - 1086 EP - 93 JF - European journal of human genetics : EJHG JO - Eur J Hum Genet VL - 13 IS - 9 N2 - Recessively inherited early-onset parkinsonism (EOP) has been associated with mutations in the Parkin, DJ-1, and PINK1 genes. We studied the prevalence of mutations in all three genes in 65 Italian patients (mean age of onset: 43.2+/-5.4 years, 62 sporadic, three familial), selected by age at onset equal or younger than 51 years. Clinical features were compatible with idiopathic Parkinson's disease in all cases. To detect small sequence alterations in Parkin, DJ-1, and PINK1, we performed a conventional mutational analysis (SSCP/dHPLC/sequencing) of all coding exons of these genes. To test for the presence of exon rearrangements in PINK1, we established a new quantitative duplex PCR assay. Gene dosage alterations in Parkin and DJ-1 were excluded using previously reported protocols. Five patients (8%; one woman/four men; mean age at onset: 38.2+/-9.7 (range 25-49) years) carried mutations in one of the genes studied: three cases had novel PINK1 mutations, one of which occurred twice (homozygous c.1602_1603insCAA; heterozygous c.1602_1603insCAA; heterozygous c.836G>A), and two patients had known Parkin mutations (heterozygous c.734A>T and c.924C>T; heterozygous c.924C>T). Family history was negative for all mutation carriers, but one with a history of tremor. Additionally, we detected one novel polymorphism (c.344A>T) and four novel PINK1 changes of unknown pathogenic significance (-21G/A; IVS1+97A/G; IVS3+38_40delTTT; c.852C>T), but no exon rearrangements. No mutations were found in the DJ-1 gene. The number of mutation carriers in both the Parkin and the PINK1 gene in our cohort is low but comparable, suggesting that PINK1 has to be considered in EOP. SN - 1018-4813 UR - https://www.unboundmedicine.com/medline/citation/15970950/PINK1_Parkin_and_DJ_1_mutations_in_Italian_patients_with_early_onset_parkinsonism_ L2 - https://medlineplus.gov/parkinsonsdisease.html DB - PRIME DP - Unbound Medicine ER -