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

Shanji Nan; Yanqiu Han; Jia Fan; Qiuhui Chen

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

VernacularTitle:中国早发性家族性阿尔茨海默病一家系淀粉样前体蛋白基因突变
Author: Shanji NAN ; Yanqiu HAN ; Jia FAN ; Qiuhui CHEN
Publication Type:Journal Article
Keywords: Alzheimer disease; Pedigree; Amyloid beta-protein precursor; Exons; Mutation
From: Chinese Journal of Neurology 2011;44(1):47-51
CountryChina
Language:Chinese
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 ε4 allele. Ⅱ9 was ε2/ε4. 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.