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

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.

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.

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).

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