Novel mutation in the PSEN2 gene (N141Y) associated with early-onset autosomal dominant Alzheimer's disease in a Chinese Han family.
The mutations in the presenilin 2 (PSEN2) gene as causes of early-onset familial Alzheimer's disease (AD) have never been reported in Asia. We conducted a phenotype and pedigree study by performing neuropathological examination and target region sequencing in a family of 3 generations. Six members in this family developed dementia in their fifth decade and died in their sixth decade. The proband was diagnosed clinically with AD, which was confirmed by an autopsy. Target region sequencing showed a novel missense mutation at codon 141 (N141Y) of the PSEN2 gene that predicts an Asparagine-to-Tyrosine substitution in the affected individuals. The result was validated by Sanger sequencing in 7 family members (2 affected and 5 unaffected). The mutation was absent in the 5 clinically unaffected relatives and 188 control subjects. No influence of the APOE genotype was observed. We are the first to demonstrate a novel PSEN2 N141Y mutation in a Chinese Han family with early-onset AD.
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Fusheng
F
Niu
BGI-Shenzhen, Shenzhen, China.
Shanshan
S
Yu
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: wuzhangzhenxin@medmail.com.cn.
Zhenxin
Z
Zhang
BGI-Shenzhen, Shenzhen, China. Electronic address: yix@genomics.cn.
Xin
X
Yi
BGI-Shenzhen, Shenzhen, China.
Lili
L
Ye
BGI-Shenzhen, Shenzhen, China.
Wei
W
Tang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Science, Chinese Academy of Medical Sciences, Beijing, China.
Changchun
C
Qiu
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Hongbo
H
Wen
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Science, Chinese Academy of Medical Sciences, Beijing, China.
Yujing
Y
Sun
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: gj107@163.com.
Jing
J
Gao
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Yupu
Y
Guo
D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001216:Asparagine / Q000235:genetics; D003062:Codon / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D053766:Presenilin-2 / Q000235:genetics*; D014443:Tyrosine / Q000235:genetics
D003062:Codon; C508861:PSEN2 protein, human; D053766:Presenilin-2; D014443:Tyrosine; D001216:Asparagine
APOE genotype; Alzheimer's disease; Chinese Han family; N141Y mutation; PSEN2; Target region sequencing