MAPT p.V363I mutation: A rare cause of corticobasal degeneration

Sarah Ahmed; Monica Diez Fairen; Marya S Sabir; Pau Pastor; Jinhui Ding; Lourdes Ispierto; Ankur Butala; Christopher M Morris; Claudia Schulte; Thomas Gasser; Edwin Jabbari; Olga Pletnikova; Huw R Morris; Juan Troncoso; Ellen Gelpi; Alexander Pantelyat; Sonja W Scholz

doi:10.1212/NXG.0000000000000347

MAPT p.V363I mutation: A rare cause of corticobasal degeneration

Neurol Genet. 2019 Jun 25;5(4):e347. doi: 10.1212/NXG.0000000000000347. eCollection 2019 Aug.

Authors

Sarah Ahmed¹, Monica Diez Fairen¹, Marya S Sabir¹, Pau Pastor¹, Jinhui Ding¹, Lourdes Ispierto¹, Ankur Butala¹, Christopher M Morris¹, Claudia Schulte¹, Thomas Gasser¹, Edwin Jabbari¹, Olga Pletnikova¹, Huw R Morris¹, Juan Troncoso¹, Ellen Gelpi¹, Alexander Pantelyat¹, Sonja W Scholz¹

Affiliation

¹ Neurodegenerative 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.

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.

Abstract

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