Presenilin 1 gene mutation p. L226R in a Chinese early-onset familial Alzheimer′s disease pedigree

Objective To analyze the clinical presentation, the mutation of the pathogenic genes and imaging features in a Chinese Han early-onset Alzheimer′s disease pedigree. Methods A pedigree of Alzheimer′s disease was collected. The DNA sequence of presenilin 1 (PSEN1), presenilin 2, micro-tubule associated protein tau, β-amyloid precursor protein gene was analyzed, the clinical presentation, results of accessory examination, neuropsychological evaluation of the proband were investigated and the point mutations of some members of the family, 50 sporadic Alzheimer′s disease patients, 50 normal controls were verified. Results The proband of the family appeared as language impairment, memory loss, personality change, repeated language, visuospatial impairment, mental and behavior disorder. The gene detection showed p. L226R mutation in the condon 226 in the exon 7 of PSEN1 gene of the proband and five other family members (Ⅲ1, Ⅲ2, Ⅲ4, Ⅲ6, Ⅲ7). The mother of the proband had the suspicious symptoms, and the sister and the brother of the proband had the similiar symptoms with the proband, all of whom died. Fifty sporadic Alzheimer′ disease patients and 50 unrelated normal subjects did not have the mutation. The computed tomographic angiography showed that the brain blood vessels were normal and 18F-fludeoxyglucose positron emission tomography (18F-FDG-PET) showed brain atrophy and hypometabolism in frontotemporal regions, parietal regions, hippocampal areas, however, the MRI, MRA and 18F-FDG-PET of the two mutation carriers (Ⅲ6, Ⅲ7) were all normal. Conclusion We reported a novel mutation in an early-onset Alzheimer′s disease family presented as language impairment in the early stage of the disease, the p. L226R mutation of PSEN1, which may be a pathogenic mutation to cause the family′s dementia. Key words: Alzheimer disease; Gene; Mutation; Presenilin-1