Probable novel PSEN2 Pro123Leu mutation in a Chinese Han family of Alzheimer's disease

We describe a probably novel mutation in exon 5 of the presenilin 2 gene (Pro123Leu) in a Chinese familial early-onset Alzheimer's disease, which clinically manifests as progressive memory loss, cognitive impairment, parkinsonism, and myoclonic jerks. Clinical and neuroimaging examination, target region capture, and high-throughput sequencing were performed in a family of 4 generations. Cerebral perfusion and glucose metabolism were evaluated using arterial spin labeling perfusion magnetic resonance imaging and 18F-fludeoxyglucose positron emission tomography, respectively. Target region capture sequencing yielded a novel missense mutation at codon 123 (P123L) which is a heterozygous C to T point mutation at position 368 (c.368C>T) in exon 5 of the presenilin 2 leading to a proline-to-leucine substitution. The results were also identified by Sanger sequencing in 7 family members but not in the other 9 unaffected family members and 100 control subjects. This mutation is probably pathogenic and is the first of its kind reported in an early-onset familial AD associated with atypical symptom presentation.