Abstract

During the past year we have published several studies identifying the extent and nature of LRRK2, PRKN and PINK mutations in Parkinson's disease. This work aims to further our understanding of the phenotypic spectrum associated with mutation in these genes. We have extended our work in the spinocerebellar ataxias by screening of TTBK2 and ITPR1 in ataxia probands (mutations in these genes were identified earlier by us to be causes of ataxia). Notably we also performed a large candidate association analysis within multiple system atrophy (MSA). This work showed for the first time that common variability in the gene SNCA is an unequivocal risk factor for MSA with an odds ratio of approximately 8. This provides critical etiologic insight into this disorder, for which no genetic risk factor had previously been identified. Our work has also included testing of the idea that OMI and GIGYF2 mutations may lead to Parkinson's disease, and analysis of DYT16, ATP13A2, PLA2G6, FBXO7 and spatacsin mutations in various young onset movement disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000957-08
Application #
8148365
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2010
Total Cost
$573,485
Indirect Cost

  Institution

Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

McMillan, Hugh J; Telegrafi, Aida; Singleton, Amanda et al. (2018) Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy. Orphanet J Rare Dis 13:86
Mendoza-Ferreira, Natalia; Coutelier, Marie; Janzen, Eva et al. (2018) Biallelic CHP1 mutation causes human autosomal recessive ataxia by impairing NHE1 function. Neurol Genet 4:e209
Coutelier, Marie; Hammer, Monia B; Stevanin, Giovanni et al. (2018) Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes. JAMA Neurol 75:591-599
Roosen, Dorien A; Singleton, Andrew B (2018) Leucine rich repeat kinase knockout (LRRK KO) mouse model: Linking pathological hallmarks of inherited and sporadic Parkinson's disease. Mov Disord 33:72
Siitonen, Maija; Börjesson-Hanson, Anne; Pöyhönen, Minna et al. (2017) Multi-infarct dementia of Swedish type is caused by a 3'UTR mutation of COL4A1. Brain :
Hammer, Monia B; Ding, Jinhui; Mochel, Fanny et al. (2017) SLC25A46 Mutations Associated with Autosomal Recessive Cerebellar Ataxia in North African Families. Neurodegener Dis 17:208-212
Urkasemsin, G; Nielsen, D M; Singleton, A et al. (2017) Genetics of Hereditary Ataxia in Scottish Terriers. J Vet Intern Med 31:1132-1139
Kun-Rodrigues, Celia; Ross, Owen A; Orme, Tatiana et al. (2017) Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies. Neurobiol Aging 49:214.e13-214.e15
Darwent, Lee; Carmona, Susana; Lohmann, Ebba et al. (2017) Mutations in TYROBP are not a common cause of dementia in a Turkish cohort. Neurobiol Aging 58:240.e1-240.e3
Guven, Gamze; Lohmann, Ebba; Bras, Jose et al. (2016) Mutation Frequency of the Major Frontotemporal Dementia Genes, MAPT, GRN and C9ORF72 in a Turkish Cohort of Dementia Patients. PLoS One 11:e0162592

Showing the most recent 10 out of 75 publications