Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease

Gao, Ying; Ren, Rong; Zhong, Zaimin; Dammer, Eric B.; Zhao, Qianhua; Shan, Shan; Zhou, Zheng; Li, Xia; Zhang, Yueqi; Cui, Hai-lun; Hu, Yongbo; Chen, Shengdi; Chen, Jianjun; Guo, Qihao; Wang, Gang

doi:10.1016/j.neurobiolaging.2019.01.018

Cited by 25 publications

(24 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The three mutations might contribute to the pathogenesis of EOAD [57,61,62]. A study on an FAD patient cohort in China was conducted by Gao et al recently, which showed that PSEN1 mutations account for the largest proportion of FAD patients, and three novel mutations in PSEN1, namely p.M139L, p.V103G, and p.F177V, were identified in the study [40]. Structural analyses indicated that these mutations might induce structural alterations in γ-secretases due to the change in interaction patterns, thereby participating in the pathogenesis of FAD [40].…”

Section: Psen1mentioning

confidence: 84%

“…Moreover, the p.K687Q mutation in APP is a likely pathogenic variant in AD, according to the standards of the American College of Medical Genetics and Genomics (ACMG) [39], while the other mutation (p.D244G) and two mutations (p.T297M and p.D332G), which were previously not associated with AD, remain uncertain with respect to their significance in the pathogenesis of AD [39]. In a similar study by Gao et al, the p.V695M mutation in APP has been found in a patient with amnestic symptoms, but the pathogenicity of this mutation needs further clarification [40]. Peng et al first reported a Chinese family with autosomal dominant EOAD caused by a heterozygous APP gene mutation (p.K724M) [41].…”

Section: Appmentioning

confidence: 99%

“…A study on an FAD patient cohort in China was conducted by Gao et al recently, which showed that PSEN1 mutations account for the largest proportion of FAD patients, and three novel mutations in PSEN1, namely p.M139L, p.V103G, and p.F177V, were identified in the study [40]. Structural analyses indicated that these mutations might induce structural alterations in γ-secretases due to the change in interaction patterns, thereby participating in the pathogenesis of FAD [40]. The p.L226R mutation of PSEN1, which is located at the transmembrane domain of the protein, was reported in an EOAD family characterized by language impairment at disease onset [59].…”

Section: Psen1mentioning

confidence: 99%

“…Gao et al found two novel variants (p.V150M and p.R163C) in PSEN2 in Chinese familial AD patients. The authors claimed that individuals carrying mutations in PSEN2 might have a relatively later disease onset compared with those with PSEN1 mutations [40]. Two novel mutations (p.N141D and p.A379D) were found to be pathogenic genetic risk factors for EOAD [66].…”

Section: Psen2mentioning

confidence: 99%

See 3 more Smart Citations

The Genetics of Alzheimer’s Disease in the Chinese Population

Gan

Zhang

Lee

2020

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. In China, the number of AD patients is growing rapidly, which poses a considerable burden on society and families. In recent years, through the advancement of genome-wide association studies, second-generation gene sequencing technology, and their application in AD genetic research, more genetic loci associated with the risk for AD have been discovered, including KCNJ15, TREM2, and GCH1, which provides new ideas for the etiology and treatment of AD. This review summarizes three early-onset AD causative genes (APP, PSEN1, and PSEN2) and some late-onset AD susceptibility genes and their mutation sites newly discovered in China, and briefly introduces the potential mechanisms of these genetic susceptibilities in the pathogenesis of AD, which would help in understanding the genetic mechanisms underlying this devastating disease.

show abstract

Section: Psen1mentioning

confidence: 84%

Section: Appmentioning

confidence: 99%

Section: Psen1mentioning

confidence: 99%

Section: Psen2mentioning

confidence: 99%

See 2 more Smart Citations

The Genetics of Alzheimer’s Disease in the Chinese Population

Gan

Zhang

Lee

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…In the present study, the PSEN1 variant (c.529T > G, p.Phe177Val) was identified in a Chinese FAD family using WES. The variant was first reported in 2019 and classified as probably pathogenic according to the standard reported by Guerreiro et al (2010) and Gao et al (2019). However, the previous study did not perform co-segregation analysis or functional study.…”

Section: Discussionmentioning

confidence: 99%

A Pathogenic Variant p.Phe177Val in PSEN1 Causes Early-Onset Alzheimer’s Disease in a Chinese Family

Jiang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Familial Alzheimer's disease (FAD) present as a positive family history of cognitive decline, with early onset and an autosomal dominant inheritance pattern. FAD is mainly caused by the mutations in the genes encoding for amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2). In the present study, we identified a variant (c.529T > G, p.Phe177Val) in PSEN1 across three generations in a Chinese family with FAD using whole-exome sequencing. The mean age of onset was 39 years (range: 37 to 40 years) in this family. In cell transfection studies, the mutant PSEN1 protein carrying p.Phe177Val increased both the production of Aβ42 and the ratio of Aβ42 over Aβ40, as compared to wild-type PSEN1. Our results confirm the pathogenicity of PSEN1 p.Phe177Val variant in FAD and broaden the clinical phenotype spectrum of FAD patients with PSEN1 p.Phe177Val variant.

show abstract

PSEN1, PSEN2, and APP mutations in 404 Chinese pedigrees with familial Alzheimer's disease

Jia

Shen

et al. 2020

Alzheimer's & Dementia

View full text Add to dashboard Cite

IntroductionThe PSENs/APP mutation distribution in Chinese patients with familial Alzheimer's disease (FAD) remains unclear. We aimed to analyze the genetic features of Chinese FAD pedigrees with and without PSENs/APP mutations.MethodsIn total, 1330 patients with Alzheimer's disease (AD) or mild cognitive impairment in 404 pedigrees were enrolled from the Chinese Familial Alzheimer's Disease Network. PSENs/APP mutations and APOE frequencies were determined.ResultsIn total, 13.12% of pedigrees carried PSENs/APP missense mutations, 3.71% carried PSENs/APP synonymous/untranslated region variants, and 83.17% did not carry PSENs/APP mutations. Eleven missense mutations were first identified. In patients without PSENs/APP mutations, 44.31% carried one APOEε4 allele, and 14.85% two APOEε4 alleles.DiscussionThe new PSENs/APP mutations indicate heterogeneity in AD pathogenesis between Chinese and other ethnic groups. The low mutation rate suggests the involvement of other genes/factors in Chinese FAD. APOEε4 might be a major gene for some FAD without PSENs/APP mutations.

show abstract

Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease

Cited by 25 publications

References 24 publications

The Genetics of Alzheimer’s Disease in the Chinese Population

The Genetics of Alzheimer’s Disease in the Chinese Population

A Pathogenic Variant p.Phe177Val in PSEN1 Causes Early-Onset Alzheimer’s Disease in a Chinese Family

PSEN1, PSEN2, and APP mutations in 404 Chinese pedigrees with familial Alzheimer's disease

Contact Info

Product

Resources

About