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

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.