title: Clinical characterization of an APP mutation (V717I) in five Han Chinese families with early-onset Alzheimer's disease.
abstract: The missense mutation V717I in amyloid precursor protein (APP) gene has been reported in many early-onset familial Alzheimer's disease (EOFAD) families. However, no detailed clinical picture regarding this mutation has ever been described for Chinese EOFAD. We investigate the age at onset (AAO), initial clinical features and non-cognitive neurological symptoms in 34 affected subjects from five Han Chinese EOFAD families with the APPV717I mutation to characterize the clinical phenotype. The AAO was 54.7±4.9years (n=34), with the APOE ɛ4 allele correlating with a decreased AAO. Prominent early affective symptoms, executive dysfunction and disorientation at onset were exhibited in 26 (76.5%), 18 (52.9%) and 16 (47%) cases, respectively. Spastic paraparesis and cerebellar ataxia occurred frequently in 13 (38.2%) and 12 (35.3%) cases, respectively, during the late stages of disease. The specific clinical phenotype of the APPV717I mutation for Chinese families is characterized by prominent early affective symptoms, executive dysfunction and disorientation as well as frequent late spastic paraparesis and cerebellar ataxia as compared to Western reports. We conclude that ethnic differences, environment or additional unknown factors may challenge the homogeneity of EOFAD with identical APP mutations.
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Guili
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, PR China; Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, PR China; Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, PR China; Key Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, PR China. Electronic address: jjp@ccmu.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000209:etiology / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D014633:Valine / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D007532:Isoleucine; D014633:Valine
keywords: APPV717I mutation; Apolipoprotein E genotype; Copy number variations; Early-onset familial Alzheimer's disease; Phenotype heterogeneity