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. F-18-fluorodeoxyglucose-positron emission tomography (PET) and C-11-2 beta-carbomethoxy-3 beta-(4-fluorophenyl) tropane-PET showed decreased metabolism and dopamine transporter distribution in the bilateral putamen and caudate nucleus. C-11-Pittsburgh compound B-PET showed beta-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.

Automated summary

A patient with a de novo mutation in PSEN1 presented with early-onset parkinsonism and mild cognitive impairment, with good response to levodopa. Brain MRI showed atrophy of the bilateral frontotemporal lobe and hippocampus. Various PET scans revealed decreased metabolism and dopamine transporter distribution in the bilateral putamen and caudate nucleus, as well as beta-amyloid protein deposition.