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
software.
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.
COL2A1 Mutation (c.611G>C) Leads to Early-Onset Osteoarthritis in a Chinese Family
