Identification of a rare amyloid precursor protein gene mutation in a Chinese family with early-onset familial Alzheimer's disease

Abstract

Objective To analyze the phenotype and genatics in a Chinese family with early-onset familial Alzheimer's disease(EOFAD). Methods Peripheral blood were collected in available members in the family and genomic DNA was extracted. PCR-sequencing of exon 16 and exon 17 of the amyloid precursor protein(APP) gene, presenilin 1 (PSEN1), and presenilin 2 (PSEN2) was performed. Results At age 40, two EOFAD patients (siblings) in the family developed an insidious onset of difficulties in memory. One ( Ⅱ3 in the pedigree) showed blinking. The other ( Ⅱ 5 ) showed irritability and bradykinesia.Progressive diffuse coritcal atrophy in bilateral temporal cortex was observed. Moderate diffuse cerebral dysfunction was observed in Ⅱ3 by the electroencephalogram study and neuropsychological assessments.Sequencing revealed that both patients were heterozygous for a mutation c. 2343 G ＞ A in exon 17 of APP,causing the amino acid substitution Val715Met. Four members ( Ⅱ1, Ⅱ 3, Ⅱ 5 and Ⅲ1 ) were homozygous for ApoE e4 allele. Ⅱ9 was e2/e4. Conclusions This study identified a mutation, Val715Met in the APP gene in Chinese patients with EOFAD. We suggest screening for APP gene mutations in Chinese patients with EOFAD. Key words: Alzheimer disease; Pedigree; Amyloid beta-protein precursor; Exons; Mutation