A novel mutation in exon 5 of the presenilin 1 gene (Gln222Leu) in a Chinese family with early-onset Alzheimer's disease has been reported, besides， it was predicted that the missense mutation was probably a novel pathogenic mutation that was reported for the first time in a Chinese family with early-onset Alzheimer's disease.
Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer's disease (EOAD).
Autosomal dominant early-onset Alzheimer's disease (EOAD) is genetically heterogeneous and has been associated with mutations in 3 different genes, coding for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2).
We found genetic etiology in 6 patients: 2 mutations in the PSEN1 gene (p.Pro264Ser and p.Phe105Cys) in the EOAD patients, C9orf72 expansion and MAPT (c.1920+16C>T), mutation in the FTD group of patients as well as MAPT (c.1920+16C>T) mutation and likely pathogenic mutation in the TYROBP mutation (p.Asp32Asn) in patients with unspecified diagnosis.
The subjects are carriers of the PSEN1 mutation, which leads to early onset Alzheimer's disease, but at the time of EEG acquisition in 1999, these subjects were cognitively unimpaired.
A minority of patients with sporadic early-onset Alzheimer's disease (AD) exhibit de novo germ line mutations in the autosomal dominant genes such as APP, PSEN1, or PSEN2.
The Val391Gly variation widens the number of PSEN1 mutations responsible for early-onset Alzheimer's disease with extrapyramidal phenotype and would help to establish a functional map of presenilin 1 protein architecture.
We conducted a comprehensive screening of rare coding variants in an African American cohort to identify novel pathogenic mutations within the early-onset Alzheimer's disease (EOAD) genes (APP, PSEN1, and PSEN2) in this understudied population.