Identification of a novel APOE mutation in one Korean male patient.

Abstract

A novel APOE mutation with Leucine-to-Proline exchange was identified in a 54-year-old Korean male patient predominantly suffering with Early Onset Alzheimer's Disease. Whole exome sequencing of the patient's DNA revealed a novel Leucine to Proline exchange of this mutation in the APOE gene. It was verified using Sanger Sequencing. It is a heterozygous ε3/ε3 T>C exchange. Protein 3D structure was created using Discovery Studio. The variant was checked in the reference databases including KRGDB, 1000Genome for its uniqueness. The mutation was screened by SIFT (Sorting Intolerant From Tolerant) and PolyPhen-2 for its pathogenicity. APOE Leu>Pro exchange could disturb the helix-4 structure of the APOE. Kyte and Doolittle Hydrophobicity scores show that this variant may be less hydrophobic. Leu > Pro exchange may result is loss of hydrophobic interactions, thus destroying the contact between Helix4 and Helix1. Leu>Pro mutation of APOE may be associated with overproduction of amyloid protein instead of amyloid clearance. Magnetic resonance imaging of the patient reveals significant medial temporal lobe atrophy as well as a decreased Clinical Dementia Rating-Sum of Boxes scores over the years from the time of onset, indicating Leu>Pro mutation may affect the progression of Tau pathology along with amyloid burden. Impact of minor APOE variants are still unclear and this novel ε3/ε3 Leu>Pro mutation may manifest clinical symptom of early onset and progression of atypical Alzheimer's Disease.