Analysis of a family with early onset familial Alzheimer′s disease caused by mutation of amyloid precursor protein gene p.V717I / 中华神经科杂志

ABSTRACT

Objective@#To analyze the clinical data of a family with early-onset familial Alzheimer′s disease and to analyze the mutation of the pathogenic gene in the family.@*Methods@#The clinical data of a proband who was clinically diagnosed as early-onset Alzheimer′s disease in the Department of Neurology, People′s Hospital of Zhengzhou University in October 2018 and her family members were collected. Moreover, whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics. Subsequently, the strong pathogenic mutation was validated by Sanger sequencing in the some members of the family and 50 sporadic Alzheimer′s disease and 50 normal individuals of the family. Apolipoprotein E (APOE) typing of 10 family members was all epsilon 3/epsilon 3.@*Results@#The proband in this family showed decreased memory, visual space disorder, verbal repetition, personality change and abnormal mental behavior. The mutation at codon 717 of exon 17 of the proband amyloid precursor protein gene was detected by gene detection. The mutation at codon 717 of exon 17 of the proband beta-amyloid precursor protein gene was also found in the other five members of the family. The mutation was not found in 50 sporadic Alzheimer′s disease patients and 50 normal individuals outside the family. The proband′s head magnetic resonance imaging (MRI) showed bilateral hippocampal atrophy on plain scan, especially on the left side. No obvious abnormality was found in the head magnetic resonance angiography. The head MRI of the proband′s sister showed brain atrophy and bilateral hippocampal atrophy.@*Conclusions@#The study identified the pathogenic mutation of the beta-amyloid precursor protein gene p.V717I in six patients of a family with early-onset familial Alzheimer′s disease, and the mutation showed a phenomenon of family segregation. This finding is of great significance to the study of early-onset Alzheimer′s disease in Chinese population.