A case of early‐onset familial Alzheimer’s disease caused by PSEN1 gene Y115C mutation in a Chinese pedigree

Abstract Background Alzheimer’s disease is the most common cause of dementia, with approximately 0.9% associated with known genetic mutations. Presenilin 1(PSEN1) gene is one of the most common genes associated with early‐onset familial Alzheimer’s disease (EOFAD). We reported a case of EOFAD with Y115C mutation of PSEN1 gene which was the first report in China. Method An early‐onset Alzheimer’s patient from Beijing Tiantan Hospital, Capital Medical University and her family were enrolled as the research object. The clinical and imaging data of the proband were collected. The genomic DNA from peripheral venous blood of the proband was screened. Result There were 6 members with memory and working competence loss in this pedigree. The proband, whose age of onset was 42 years old, was manifested as memory loss for more than 1year. She became apathetic, lazy in housework but without abnormal mood and behavior. She was healthy in the past, denied smoking and drinking history. Her grandmother, mother, aunt, uncle and brother all showed memory loss. Her brother is now unable to complete the driver’s work. The physical examination showed poor memory, calculation, orientation, executive functions, slow reaction and poor comprehension. The MMSE score was 11, MoCA‐Beijing score was 5, ADL‐20 score was 28, HAMD score was 2, HAMA score was 1 and PSQI score was 5. Head MRI of the proband showed whole cerebral cortical atrophy and bilateral hippocampal atrophy, obviously on the left side. The arterial spin labeling finding showed significantly reduced blood perfusion in the left cortex and hippocampus. A c.344A > G (p. Tyr115Cys) pathogenic mutation in the exon 5 of PSEN1 gene was found, proving the diagnosis. Conclusion We reported this EOFAD case caused by Y115C mutation of PSEN1 gene in a Chinese family to enrich the genetic and clinical phenotypic characteristics in China. Gene detection plays an important role in the diagnosis of the early‐onset Alzheimer’s disease.