Background：The rate of occurrence of Alzheimer’s disease is increasing around the world.
However, there is still no significant breakthrough in the study of its etiology and pathogenesis.
Objective：To screen Alzheimer's disease pathogenic genes, which may be conducive to the elucidation
of the pathogenic mechanisms of Alzheimer's disease And predict the pathogenicity by various computer
Method：Clinical and neuroimaging examination, Whole Exome Sequencing, and Sanger sequencing
were performed in the proband. Mutation sites were verified in 158 subjects.
Results：We reported a proband carrying a probably novel pathogenic mutation, which clinically manifests
as progressive memory loss, visual-spatial disorders, apraxia, psychobehavioral disorders, and
temperamental and personality changes. Whole Exome Sequencing detected a novel missense mutation
at codon 222 (Q222L), which is a heterozygous A to T point mutation at position 665 (c.665A>T) in
exon 5 of the presenilin 1 leading to a glutamine-to-leucine substitution. The mutation was also identified
by Sanger sequencing in one family member; nevertheless, it was not detected in the other 7 unaffected
family members, 50 sporadic Alzheimer's disease patients and 100 control subjects.
Conclusion：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.