Mutation screening in Chinese patients with familial Alzheimer's disease by whole-exome sequencing

Jiang, Bin; Zhou, Jiong; Li, Honglei; Chen, Yangui; Cheng, Hong-Rong; Ye, Lingqi; Li, Deshan; Chen, Dian-Fu; Tao, Qing‐Qing; Wu, Zhi‐Ying

doi:10.1016/j.neurobiolaging.2018.11.024

Cited by 35 publications

(40 citation statements)

References 44 publications

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“…This mutation was previously reported as a causative mutation of FAD. The pedigree in Germany composed of six affected individuals over multiple generations, who presented with highly homogenous phenotypes with the onset of cognitive impairment around 30 years of age, followed by myoclonus and epileptic seizures.…”

Section: Discussionmentioning

confidence: 99%

Sporadic progressive myoclonic epilepsy with early‐onset dementia caused by a de novo mutation in PSEN1

Taminato

Araki

Sato

et al. 2019

Neurology & Clinical Neurosc

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Progressive myoclonic epilepsy contains wide variety of diseases in which differential diagnosis is challenging. Here, we report a 36 year‐old female patient presenting with sporadic myoclonic epilepsy and cognitive decline. Cerebrospinal fluid analysis revealed increased level of total tau and phosphorylated tau and decreased level of amyloid beta‐42 protein, although the extent was modest. Whole‐exome sequencing analysis revealed a known heterozygous de novo mutation p.Phe177Ser in PSEN1, a causative gene for familial Alzheimer's disease. A previously reported pedigree with the same mutation presented with similar phenotypes, indicating genotype‐phenotype correlation. This report illustrated that familial Alzheimer's disease with PSEN1 mutations should be considered in the differential diagnosis of progressive myoclonus epilepsy.

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Section: Discussionmentioning

confidence: 99%

Sporadic progressive myoclonic epilepsy with early‐onset dementia caused by a de novo mutation in PSEN1

Taminato

Araki

Sato

et al. 2019

Neurology & Clinical Neurosc

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“…Patients who exhibit agnogenic white matter abnormality, unexplained spastic paraparesis, or early‐onset dementia were suggestive of leukodystrophies . Firstly we screened causative genes for CADASIL, adrenoleukodystrophy, hereditary spastic paraplegia (HSP), and familial Alzheimer's disease (FAD) on these patients in our previous studies, and patients who carry pathogenic variants were excluded. Then, 28 unrelated patients (probands) were recruited consecutively between March 2015 and August 2018 from the Department of Neurology in Second Affiliated Hospital of Zhejiang University School of Medicine.…”

Section: Methodsmentioning

confidence: 99%

New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies

et al. 2019

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Aim Leukodystrophies are a group of inherited white matter disorders with clinical, genetic, and imaging heterogeneity, which usually pose a diagnostic challenge for physicians. We aimed to identify new clinical characteristics and novel pathogenic variants of hereditary leukodystrophies in this study. Methods Whole exome sequencing (WES) was performed in 28 unrelated patients clinically suspected with leukodystrophies. Leukocytes enzyme activity test, electroencephalogram (EEG), electromyography (EMG), and brain MRI were conducted. Functional analysis was performed, and the pathogenicity of variants was classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Results We made definite diagnosis in 8 probands with 12 pathogenic variants and reported new clinical characteristics and imaging features of these patients. Three novel pathogenic variants were identified, including a microdeletion variant c.2654_2654+3del within CSF1R, a nonsense variant c.1321C>T, and a missense variant c.166G>C within GALC. Conclusion Our results have deepened the understanding of clinical, genetic, and imaging heterogeneity of hereditary leukodystrophies, and expanded the spectrum of pathogenic variants and clinical features.

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“…In addition to the reported APP gene mutations (p.V717I), they discovered two novel mutations in APP (p.D244G and p.K687Q) [39]. 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].…”

Section: Appmentioning

confidence: 99%

“…Three APP polymorphisms at codons 710, 718, and 720 with single nucleotide substitutions (corresponding to V710G, I718L and L720S) were found first in Taiwanese patients associated with Chinese/Taiwanese patients with AD in 2009 [38]. Jiang et al carried out whole-exome screening to identify the gene mutations of APP, PSEN1, and PSEN2 in a small group of Chinese FAD patients [39]. In addition to the reported APP gene mutations (p.V717I), they discovered two novel mutations in APP (p.D244G and p.K687Q) [39].…”

Section: Appmentioning

confidence: 99%

“…Jiang et al carried out whole-exome screening to identify the gene mutations of APP, PSEN1, and PSEN2 in a small group of Chinese FAD patients [39]. In addition to the reported APP gene mutations (p.V717I), they discovered two novel mutations in APP (p.D244G and p.K687Q) [39]. 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].…”

Section: Appmentioning

confidence: 99%

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The Genetics of Alzheimer’s Disease in the Chinese Population

Gan

Zhang

Lee

2020

IJMS

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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.

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Mutation screening in Chinese patients with familial Alzheimer's disease by whole-exome sequencing

Cited by 35 publications

References 44 publications

Sporadic progressive myoclonic epilepsy with early‐onset dementia caused by a de novo mutation in PSEN1

Sporadic progressive myoclonic epilepsy with early‐onset dementia caused by a de novo mutation in PSEN1

New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies

The Genetics of Alzheimer’s Disease in the Chinese Population

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