Evaluation of the Clinical Features Accompanied by the Gene Mutations: The 2 Novel PSEN1 Variants in a Turkish Early-onset Alzheimer Disease Cohort

Abstract

Introduction: Early-onset Alzheimer disease (EOAD) is an earlier Alzheimer disease form which is characterized by the mutations in the amyloid precursor protein, presenilin-1/2 (PSEN1/2), and triggering receptor expressed on myeloid cells 2 (TREM2). However, it is still necessary to report mutational screening in multiethnic groups to improve the genetic background of EOAD due to the variant classification challenge.

Methods: We performed targeted sequencing for the amyloid precursor protein, PSEN1, PSEN2, and TREM2 genes in 74 patients and 1 family diagnosed with EOAD.

Results: Among the detected variants, 8 were coding and 6 were noncoding in 15 of 74 patients. In PSEN1, 2 pathogenic coding variants (T274K and L364P) detected in 2 patients were novel and 3 coding variants (G183V, E318G, and L219P) detected in 2 patients were previously reported. We found 4 patients with the compound heterozygosity for the PSEN2 A23= and N43= and a family with the coexistence of them, and 1 patient with TREM2 Y38C. The coding variation frequency was 12.1%. In silico analysis indicated pathogenic potentials and clinical interpretations of the detected variants.

Conclusion: Our study reveals the rare gene variants including novel ones from the Turkish EOAD cohort and provides to clinicians the list of detected variants in the screened genes, which may also be useful for accurate genetic counseling.