@article{e74d2fbe6d9344c9a868e0fa373e3286,
title = "MAPT p.V363I mutation A rare cause of corticobasal degeneration",
abstract = "Objective Patients with corticobasal syndrome (CBS) present with heterogeneous clinical features, including asymmetric parkinsonism, dyspraxia, aphasia, and cognitive impairment; to better understand the genetic etiology of this rare disease, we undertook a genetic analysis of microtubule-associated protein tau (MAPT). Methods We performed a genetic evaluation of MAPT mutations in 826 neurologically healthy controls and 173 cases with CBS using the Illumina NeuroChip genotyping array. Results We identified 2 patients with CBS heterozygous for a rare mutation in MAPT (p.V363I) that is located in the highly conserved microtubule-binding domain. One patient was pathologically confirmed and demonstrated extensive 4-repeat-tau-positive thread pathology, achromatic neurons, and astrocytic plaques consistent with corticobasal degeneration (CBD). Conclusions We report 2 CBS cases carrying the rare p.V363I MAPT mutation, one of which was pathologically confirmed as CBD. Our findings support the notion that this rare coding change is pathogenic.",
author = "Sarah Ahmed and Fairen, {Monica Diez} and Sabir, {Marya S.} and Pau Pastor and Jinhui Ding and Lourdes Ispierto and Ankur Butala and Morris, {Christopher M.} and Claudia Schulte and Thomas Gasser and Edwin Jabbari and Olga Pletnikova and Morris, {Huw R.} and Juan Troncoso and Ellen Gelpi and Alexander Pantelyat and Scholz, {Sonja W.}",
note = "Funding Information: The Article Processing Charge was funded by the NIH. Funding Information: This work was supported in part by the Intramural Research Programs of the NINDS and the National Institute on Aging (NIA) (project numbers Z01-AG000949 and 1ZIA NS003154). This study was partially supported by a CurePSP research grant (Cure PSP grant no.: 515-14; 2013-2015) to PP. EG received support from a grant from the Marat{\'o} de TV3 (grant no. 20141610). Funding Information: The authors thank all the subjects who donated their time and biological samples to be a part of this study. They thank the NIH NeuroBrainBank and the IDIBAPS Brain Bank, Barcelona, Spain, for contributing brain tissue samples. This study used tissue samples and data provided by the Michigan Brain Bank, the Michigan Alzheimer's Disease Center (5P30 AG053760), and the Protein Folding Disorders Program. This study used samples from the NINDS Repository at Coriell ( catalog.coriell.org ) and clinical data. The authors are grateful to the Banner Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona, for the provision of human brain tissue. The Brain and Body Donation Program is supported by the NINDS (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-0901, and 1001 to the Arizona Parkinson's Disease Consortium), and the Michael J. Fox Foundation for Parkinson's Research. The authors thank the Kathleen Price Bryan Brain Bank at Duke University Medical Center, the Harvard Brain Bank, and the Georgetown University Brain Bank for the provision of tissue and DNA samples. Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074), by NIHR Newcastle Biomedical Research Centre and Unit awarded to the Newcastle upon Tyne NHS Foundation Trust and Newcastle University, and as part of the Brains for Dementia Research Programme jointly funded by Alzheimer's Research UK and Alzheimer's Society. The authors thank members of the North American Brain Expression Consortium for providing DNA samples on neurologically healthy controls. Tissue samples for genotyping were provided by the Johns Hopkins Morris K. Udall Center of Excellence for Parkinson's Disease Research (NIH P50 NS38377) and the Johns Hopkins Alzheimer Disease Research Center (NIH P50 AG05146).",
year = "2019",
month = aug,
day = "1",
doi = "10.1212/NXG.0000000000000347",
language = "English (US)",
volume = "5",
journal = "Neurology: Genetics",
issn = "2376-7839",
publisher = "Lippincott Williams and Wilkins",
number = "4",
}