A heterozygous de novo PSEN1 mutation in a patient with early-onset parkinsonism.

BACKGROUND

Mutations in presenilin 1 (PSEN1) are the most common known genetic cause of early-onset Alzheimer's disease. Patients with PSEN1 mutations exhibit broad phenotypes. Here, we report clinical, neuroimaging and genetic findings in a patient with a de novo mutation in PSEN1 (c.697A > G, p.M233V) presenting with early-onset parkinsonism as the initial and primary symptom.

METHODS

We recruited a family with one affected patient with early-onset parkinsonism. The patient underwent comprehensive neurological examination and imaging evaluation. Whole genome sequencing was performed for the proband.

RESULTS

The patient presented with parkinsonism and mild cognitive impairment. He had a good response to levodopa. Brain MRI evaluation showed atrophy of the bilateral frontotemporal lobe and hippocampus. 18F-fluorodeoxyglucose-positron emission tomography (PET) and 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane-PET showed decreased metabolism and dopamine transporter distribution in the bilateral putamen and caudate nucleus. 11C-Pittsburgh compound B -PET showed β-amyloid protein deposition. Genetic analysis identified a heterozygous de novo variant in PSEN1 (c.697A > G, p.M233V).

CONCLUSIONS

Screening for PSEN1 variations should be considered in patients with levodopa-responsive early-onset parkinsonism.