Related Experiment Video
Updated: Jan 21, 2026

Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
Published on: August 24, 2017
MAPT p.V363I mutation: A rare cause of corticobasal degeneration
Sarah Ahmed1, Monica Diez Fairen1, Marya S Sabir1
1Neurodegenerative Disease Research Unit (S.A., M.S.S., S.W.S.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Movement Disorders and Memory Unit (M.D.F., P.P.), Department of Neurology, University Hospital Mutua de Terrassa, and Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Barcelona, Spain; Laboratory of Neurogenetics (J.D.), National Institutes on Aging, National Institutes of Health, Bethesda, MD; Neurology Service (L.I.), Hospital Universitari Germans Trias, Pujol, Badalona, Spain; Department of Neurology (A.B., A.P., S.W.S.), Johns Hopkins University Medical Center, Baltimore, MD; Newcastle Institute for Ageing (C.M.M.), Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Neurodegenerative Diseases (C.S., T.G.), Center of Neurology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, and German Center for Neurodegenerative Diseases, Germany; Department of Molecular and Clinical Neuroscience (E.J., H.R.M.), Institute of Neurology, University College London, United Kingdom; Department of Pathology (Neuropathology) (O.P., J.T.), Johns Hopkins University Medical Center, Baltimore, MD; Department of Clinical Neurosciences (H.R.M.), Royal Free Campus UCL, Institute of Neurology, London, United Kingdom; Neurological Tissue Bank (E.G.), University of Barcelona-Hospital Clinic, IDIBAPS, Barcelona, Spain; and Institute of Neurology (E.G.), Medical University of Vienna, Austria.
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.
Related Concept Videos
Mutations
Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Viral Mutations
Mutation, Gene Flow, and Genetic Drift
Mutations in Microorganisms
Point and Frameshift Mutations

