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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.

SUBMITTER: Ahmed S

PROVIDER: S-EPMC6659135 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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<i>MAPT</i> p.V363I mutation: A rare cause of corticobasal degeneration.

Ahmed Sarah S Fairen Monica Diez MD Sabir Marya S MS Pastor Pau P Ding Jinhui J Ispierto Lourdes L Butala Ankur A Morris Christopher M CM Schulte Claudia C Gasser Thomas T Jabbari Edwin E Pletnikova Olga O Morris Huw R HR Troncoso Juan J Gelpi Ellen E Pantelyat Alexander A Scholz Sonja W SW

Neurology. Genetics 20190625 4

<h4>Objective</h4>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 (<i>MAPT</i>).<h4>Methods</h4>We performed a genetic evaluation of <i>MAPT</i> mutations in 826 neurologically healthy controls and 173 cases with CBS using the Illumina NeuroChip ...[more]

PMID: 31404212

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Project description:Patients with corticobasal degeneration can present with several different clinical syndromes, making ante-mortem diagnosis a challenge. Corticobasal syndrome is the clinical phenotype originally described for corticobasal degeneration, characterized by asymmetric rigidity and apraxia, cortical sensory deficits, dystonia and myoclonus. Some patients do not develop these features, but instead have clinical features consistent with the Richardson syndrome presentation of progressive supranuclear palsy, characterized by postural instability, early unexplained falls, vertical supranuclear gaze palsy, symmetric motor disability and dysphagia. The aim of this study was to identify differences in corticobasal degeneration presenting with corticobasal syndrome (n = 11) or Richardson syndrome (n = 15) with respect to demographic, clinical and neuropathological features. Corticobasal degeneration cases were also compared with patients with pathologically proven progressive supranuclear palsy with Richardson syndrome (n = 15). Cases with corticobasal degeneration, regardless of presentation, shared histopathological and tau biochemical characteristics, but they had differing densities of tau pathology in neuroanatomical regions that correlated with their clinical presentation. In particular, those with corticobasal syndrome had greater tau pathology in the primary motor and somatosensory cortices and putamen, while those with Richardson syndrome had greater tau pathology in limbic and hindbrain structures. Compared with progressive supranuclear palsy, patients with corticobasal degeneration and Richardson syndrome had less neuronal loss in the subthalamic nucleus, but more severe neuronal loss in the medial substantia nigra and greater atrophy of the anterior corpus callosum. Clinically, they had more cognitive impairment and frontal behavioural dysfunction. The results suggest that Richardson syndrome can be a clinicopathological presentation of corticobasal degeneration. Atrophy of anterior corpus callosum may be a potential neuroimaging marker to differentiate corticobasal degeneration from progressive supranuclear palsy in patients with Richardson syndrome.

Dataset Information

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

Publications

<i>MAPT</i> p.V363I mutation: A rare cause of corticobasal degeneration.

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