A novel PSEN1 H163P mutation in a patient with early-onset Alzheimer's disease: Clinical, neuroimaging, and neuropathological findings

We report a novel presenilin 1 gene (PSEN1) mutation (H163P) in a patient with sporadic early-onset Alzheimer's disease. Clinical, molecular, and neuropathological examinations were performed on an index patient, who presented at the age of 34 years with depression and memory disturbances. At the age of 36 years, she exhibited seizures and myoclonus, cerebellar ataxia, and Parkinsonism. A novel mutation at codon 163 was found in PSEN1, which was changed from histidine to proline. Severe atrophy was noted in the frontal and temporal lobes of the brain. A histopathological examination of the frontal cortex revealed senile plaques and severe neurofibrillary tangles. PSEN1 codon 163 could be a mutational hot spot in early-onset Alzheimer's disease, and may result in a homogeneous phenotype similar to that of other patients with codon-163 mutations; thus, widening the spectrum of PSEN1 codon-163-linked phenotypes.

► We found novel PSEN1 H163P mutation in a patient with an early-onset Alzheimer's disease. ► We confirmed the AD pathology in the patient with PSEN1 H163P mutation. ► We described the phenotype of a patient with EOAD, the PSEN1 H163P mutation. ► Our results suggested that PSEN1 codon 163 could be mutational hot spot in EOAD.