Mutations in DJ-1 Are Rare in Familial Parkinson Disease

Overview

Journal Neurosci Lett

Specialty Neurology

Date 2006 Sep 26

PMID 16997464

Citations 17

Authors

Nathan Pankratz

Michael W Pauciulo

Veronika E Elsaesser

Diane K Marek

Cheryl A Halter

Joanne Wojcieszek

Alice Rudolph

Clifford W Shults

Tatiana Foroud

William C Nichols

Affiliations

Soon will be listed here.

Abstract

Mutations in DJ-1 (PARK7) are one cause of early-onset autosomal-recessive parkinsonism. We screened for DJ-1 mutations in 93 affected individuals from the 64 multiplex Parkinson disease (PD) families in our sample that had the highest family-specific multipoint LOD scores at the DJ-1 locus. In addition to sequencing all coding exons for alterations, we used multiplex ligation-dependent probe amplification (MLPA) to examine the genomic copy number of DJ-1 exons. A known polymorphism (R98Q) was found in five PD subjects, once as a homozygote and in the other four cases as heterozygotes. No additional missense mutations and no exon deletions or duplications were detected. Our results, in combination with those of previous studies, suggest that alterations in DJ-1 are not a common cause of familial PD.

Citing Articles

Evolving Landscape of Parkinson's Disease Research: Challenges and Perspectives.

Tenchov R, Sasso J, Zhou Q ACS Omega. 2025; 10(2):1864-1892.

PMID: 39866628 PMC: 11755173. DOI: 10.1021/acsomega.4c09114.

Pain in monogenic Parkinson's disease: a comprehensive review.

Alizadeh P, Terroba-Chambi C, Achen B, Bruno V Front Neurol. 2023; 14:1248828.

PMID: 38020640 PMC: 10643218. DOI: 10.3389/fneur.2023.1248828.

Immune Response Modifications in the Genetic Forms of Parkinson's Disease: What Do We Know?.

Magistrelli L, Contaldi E, Vignaroli F, Gallo S, Colombatto F, Cantello R Int J Mol Sci. 2022; 23(7).

PMID: 35408836 PMC: 8998358. DOI: 10.3390/ijms23073476.

DJ-1 depletion prevents immunoaging in T-cell compartments.

Zeng N, Capelle C, Baron A, Kobayashi T, Cire S, Tslaf V EMBO Rep. 2022; 23(3):e53302.

PMID: 35037711 PMC: 8892345. DOI: 10.15252/embr.202153302.

Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.

Chandler R, Cogo S, Lewis P, Kevei E Biosci Rep. 2021; 41(9).

PMID: 34397087 PMC: 8415217. DOI: 10.1042/BSR20203672.

References

Hering R, Strauss K, Tao X, Bauer A, Woitalla D, Mietz E . Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7). Hum Mutat. 2004; 24(4):321-9. DOI: 10.1002/humu.20089. View

Lockhart P, Bounds R, Hulihan M, Kachergus J, Lincoln S, Lin C . Lack of mutations in DJ-1 in a cohort of Taiwanese ethnic Chinese with early-onset parkinsonism. Mov Disord. 2004; 19(9):1065-9. DOI: 10.1002/mds.20082. View

Hughes A, Daniel S, Kilford L, Lees A . Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992; 55(3):181-4. PMC: 1014720. DOI: 10.1136/jnnp.55.3.181. View

de Rijk M, Tzourio C, Breteler M, Dartigues J, Amaducci L, Lopez-Pousa S . Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson's disease. J Neurol Neurosurg Psychiatry. 1997; 62(1):10-5. PMC: 486688. DOI: 10.1136/jnnp.62.1.10. View

Gasser T . Genetics of Parkinson's disease. Curr Opin Neurol. 2005; 18(4):363-9. DOI: 10.1097/01.wco.0000170951.08924.3d. View

Klein C, Djarmati A, Hedrich K, Schafer N, Scaglione C, Marchese R . PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism. Eur J Hum Genet. 2005; 13(9):1086-93. DOI: 10.1038/sj.ejhg.5201455. View

Karamohamed S, Golbe L, Mark M, Lazzarini A, Suchowersky O, Labelle N . Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study. Mov Disord. 2005; 20(9):1188-91. DOI: 10.1002/mds.20515. View

Annesi G, Savettieri G, Pugliese P, DAmelio M, Tarantino P, Ragonese P . DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex. Ann Neurol. 2005; 58(5):803-7. DOI: 10.1002/ana.20666. View

Guo J, Tang B, Zhang Y, Xia K, Cai F, Pan Q . [Mutation analysis of DJ1 gene in patients with autosomal recessive early-onset Parkinsonism]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005; 22(6):641-3. View

10.

van Duijn C, Dekker M, Bonifati V, Galjaard R, Houwing-Duistermaat J, Snijders P . Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36. Am J Hum Genet. 2001; 69(3):629-34. PMC: 1235491. DOI: 10.1086/322996. View

11.

Hughes A, Ben-Shlomo Y, Daniel S, Lees A . What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. 1992. Neurology. 2002; 57(10 Suppl 3):S34-8. View

12.

Bonifati V, Rizzu P, van Baren M, Schaap O, Breedveld G, Krieger E . Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2002; 299(5604):256-9. DOI: 10.1126/science.1077209. View

13.

Foroud T, Uniacke S, Liu L, Pankratz N, Rudolph A, Halter C . Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology. 2003; 60(5):796-801. DOI: 10.1212/01.wnl.0000049470.00180.07. View

14.

Hague S, Rogaeva E, Hernandez D, Gulick C, Singleton A, Hanson M . Early-onset Parkinson's disease caused by a compound heterozygous DJ-1 mutation. Ann Neurol. 2003; 54(2):271-4. DOI: 10.1002/ana.10663. View

15.

Abou-Sleiman P, Healy D, Quinn N, Lees A, Wood N . The role of pathogenic DJ-1 mutations in Parkinson's disease. Ann Neurol. 2003; 54(3):283-6. DOI: 10.1002/ana.10675. View

16.

Ibanez P, De Michele G, Bonifati V, Lohmann E, Thobois S, Pollak P . Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism. Neurology. 2003; 61(10):1429-31. DOI: 10.1212/01.wnl.0000094121.48373.fd. View

17.

Hedrich K, Schafer N, Hering R, Hagenah J, Lanthaler A, Schwinger E . The R98Q variation in DJ-1 represents a rare polymorphism. Ann Neurol. 2004; 55(1):145. DOI: 10.1002/ana.10816. View

18.

Healy D, Abou-Sleiman P, Valente E, Gilks W, Bhatia K, Quinn N . DJ-1 mutations in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004; 75(1):144-5. PMC: 1757445. View

19.

Hedrich K, Djarmati A, Schafer N, Hering R, Wellenbrock C, Weiss P . DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology. 2004; 62(3):389-94. DOI: 10.1212/01.wnl.0000113022.51739.88. View

20.

Lockhart P, Lincoln S, Hulihan M, Kachergus J, Wilkes K, Bisceglio G . DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function. J Med Genet. 2004; 41(3):e22. PMC: 1735689. DOI: 10.1136/jmg.2003.011106. View