Pathogenic <i>PSEN1</i> Thr119Ile Mutation in Two Korean Patients with Early-Onset Alzheimer’s Disease
Eva Bagyinszky,
Hyon Lee,
Jung Min Pyun,
Jeewon Suh,
Min Ju Kang,
Van Giau Vo,
Seong Soo A. An,
Kee Hyung Park,
SangYun Kim
Affiliations
Eva Bagyinszky
Department of Industrial and Environmental Engineering, Graduate School of Environment Gachon University, Seongnam 13120, Korea
Hyon Lee
Department of Neurology, Gachon University Gil Medical Center, Incheon 21565, Korea
Jung Min Pyun
Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Jeewon Suh
Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Min Ju Kang
Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Korea
Van Giau Vo
Institute of Research and Development, Duy Tan University, Danang 550000, Vietnam
Seong Soo A. An
Department of Bionano Technology, Gachon University, Seongnam 13120, Korea
Kee Hyung Park
Department of Neurology, Gachon University Gil Medical Center, Incheon 21565, Korea
SangYun Kim
Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam 13620, Korea
We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed diffuse atrophy in the fronto-parietal regions. In addition, 18F-fludeoxyglucose positron emission tomography (FDG-PET) showed reduced tracer uptake in the parietal and temporal cortices, bilaterally. The second patient developed memory dysfunction at the age of 49, and his mother was also affected. Amyloid positron emission tomography (PET) was positive, but MRI scans did not reveal any atrophy. Targeted NGS and Sanger sequencing identified a heterozygous C to T exchange in PSEN1 exon 5 (c.356C>T), resulting in a p.Thr119Ile mutation. The mutation is located in the conserved HL-I loop, where several Alzheimer’s disease (AD) related mutations have been described. Structure analyses suggested that Thr119Ile mutation may result in a significant change inside conservative loop. Additional in vitro studies are needed to estimate the role of the PSEN1 Thr119Ile in AD disease progression.
