Mutational analysis in early-onset familial Alzheimer's disease in Mainland China.

Abstract

Mutations of 3 causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early-onset familial Alzheimer's disease (EOFAD). Recently, a GGGGCC repeat expansion in the noncoding region of C9orf72 was also detected in some patients with clinically diagnosed familial Alzheimer's disease. The prevalence of causative gene mutations in patients with EOFAD has been reported in previous studies but their prevalence remains unclear in Mainland China. The aim of this study was to characterize the common causative gene mutation spectrum and genotype-phenotype correlations in Chinese patients with EOFAD. Genetic screening for mutations in PSEN1, PSEN2, and APP was conducted in a total of 32 families with clinical diagnoses of EOFAD from Mainland China. Subsequently, a hexanucleotide repeat expansion in C9orf72 was detected in all patients. Four novel mutations in PSEN1 (p.A434T, p.I167del, p.F105C, and p.L248P) were identified in 4 respective families, and 1 previously recognized pathogenic mutation in APP (p.V717I) was detected in another 2 unrelated families. The PSEN2 mutation and pathogenic repeat expansions of C9orf72 were not detected in all patients. To the best of our knowledge, this is the first cohort report of a causative gene screen in patients with EOFAD in Mainland China. The analysis of the genetic-clinical correlations in this cohort supports the idea that the clinical phenotype might be influenced by specific genetic defects.

• Authors: Bin Jiao, Beisha Tang, Xiaoyan Liu, Jun Xu, Yanjiang Wang, Lin Zhou, Fufeng Zhang, Xinxiang Yan, Yafang Zhou, Lu Shen
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 35 Issue 8 Pg. 1957.e1-6 (Aug 2014) ISSN: 1558-1497 [Electronic] United States
• PMID: 24650794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Protein Precursor
• Apolipoproteins E
• C9orf72 Protein
• C9orf72 protein, human
• PSEN1 protein, human
• PSEN2 protein, human
• Presenilin-1
• Presenilin-2
• Proteins

Topics

• Age of Onset
• Aged
• Alzheimer Disease (epidemiology, genetics)
• Amyloid beta-Protein Precursor (genetics)
• Apolipoproteins E (genetics)
• C9orf72 Protein
• China (epidemiology)
• Cohort Studies
• DNA Mutational Analysis
• DNA Repeat Expansion
• Female
• Genetic Association Studies
• Genetic Testing
• Genotype
• Humans
• Male
• Middle Aged
• Mutation
• Presenilin-1 (genetics)
• Presenilin-2 (genetics)
• Prevalence
• Proteins (genetics)