A novel presenilin 1 mutation (Ser169del) in a Chinese family with early-onset Alzheimer's disease

Guo, Jifeng; Wei, Jiaohua; Liao, Shusheng; Wang, Lei; Jiang, Hong; Tang, Beisha

doi:10.1016/j.neulet.2009.10.055

Cited by 24 publications

(11 citation statements)

References 25 publications

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“… 16 , 17 , 27 , 28 , 55 , 66 – 68 In the People’s Republic of China, most of the PSEN1 variants, such as Ile167del, Ser169del, and Leu248Pro, were newly discovered. 12 , 43 , 44 PSEN2 mutation was rare in Asian countries; however, novel Val214Leu, His169Asn, and Asn141Tyr mutations were found. PSEN2 Arg62Cys mutation, which was initially discovered in Belgian Caucasians, was found among Korean.…”

Section: Discussionmentioning

confidence: 96%

“…Family history was positive, since her deceased father was diagnosed with AD and her younger brother was also affected by this mutation and showed similar clinical symptoms. 44 Arg352Cys (CGC→TGC) was reported in three members of a Han family. This mutation might not segregate with the disease onset, since this mutation was also found in an unaffected individual.…”

Section: App Psen1 and Psenmentioning

confidence: 97%

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Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Bagyinszky

Youn

et al. 2016

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Alzheimer’s disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People’s Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People’s Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.

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Section: Discussionmentioning

confidence: 96%

Section: App Psen1 and Psenmentioning

confidence: 97%

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Bagyinszky

Youn

et al. 2016

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“…To test whether our chemical induction protocol can be applied to generate hciNs for modeling of neurological diseases, we induced neuronal conversion of human skin fibroblasts derived from patients with familial Alzheimer's disease (FAD) carrying mutations in APP (V717I) or presenilin 1 (I167del or A434T or S169del) (Guo et al, 2010;Jiao et al, 2014). The hciNs derived from FAD fibroblasts displayed similar neuronal characteristics to those of hciNs derived from normal fibroblasts ( Figure 4A).…”

Section: Generation Of Hcins From Fad Patient Fibroblastsmentioning

confidence: 99%

Direct Conversion of Normal and Alzheimer’s Disease Human Fibroblasts into Neuronal Cells by Small Molecules

et al. 2015

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Neuronal conversion from human fibroblasts can be induced by lineage-specific transcription factors; however, the introduction of ectopic genes limits the therapeutic applications of such induced neurons (iNs). Here, we report that human fibroblasts can be directly converted into neuronal cells by a chemical cocktail of seven small molecules, bypassing a neural progenitor stage. These human chemical-induced neuronal cells (hciNs) resembled hiPSC-derived neurons and human iNs (hiNs) with respect to morphology, gene expression profiles, and electrophysiological properties. This approach was further applied to generate hciNs from familial Alzheimer's disease patients. Taken together, our transgene-free and chemical-only approach for direct reprogramming of human fibroblasts into neurons provides an alternative strategy for modeling neurological diseases and for regenerative medicine.

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“… 86–94 Yes Pathogenic by in silico [ 20 ] Sassi et al, 2014 S169del (ΔS169, Ser169del, ΔS170) MRI revealed cerebral atrophy involvement of the ventricles and widening of the sulci. 40 Yes Not available [ 28 ] Guo et al, 2010 S169 L Aβ deposition in the cerebellum and white matter 33–37 Yes Not available [ 29 ] Taddei et al, 1998 S169P Numerous plaques and neurofibrillary tangles could be seen in brain of the case 35 Yes Not available [ 30 ] Ezquerra et al, 1999 S170F Much Lewy bodies in the substantia nigra and had severe cerebellar pathology Also, abundant amyloid deposition and loss of Purkinje cells reported. 27 Yes ↑Aβ42 and Aβ40, altering the ratio.…”

Section: Discussionmentioning

confidence: 99%

A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimer’s disease

et al. 2019

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Background: Presenilin-1 (PSEN1) is one of the causative genes for early onset Alzheimer's disease (EOAD). Recently, emerging studies reported several novel PSEN1 mutations among Asian. We describe a male with EOAD had a pathogenic PSEN1 mutation. Case presentation: A 53-year-old male presented with memory decline, followed by difficulty in finding ways. Patient had positive family history, since his mother and one of his brother was also affected with dementia. Brain magnetic resonance imaging (MRI) scan showed mild degree of atrophy of bilateral hippocampus and parietal lobe. 18 F-Florbetaben-PET (FBB-PET) revealed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and precuneus. Whole exome analysis revealed a heterozygous, probably pathogenic PSEN1 (c.695G > T, p.W165C) mutation. Interestingly, Trp165Cys mutation is located in trans membrane (TM)-III region, which is conserved between PSEN1/PSEN2. In vitro studies revealed that PSEN1 Trp165Cys could result in disturbances in amyloid metabolism. This prediction was confirmed by structure predictions and previous in vitro studies that the p.Trp165Cys could result in decreased Aβ42/Aβ40 ratios. Conclusion: We report a case of EOAD having a pathogenic PSEN1 (Trp165Cys) confirmed with in silico and in vitro predictions.

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A novel presenilin 1 mutation (Ser169del) in a Chinese family with early-onset Alzheimer's disease

Cited by 24 publications

References 25 publications

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Direct Conversion of Normal and Alzheimer’s Disease Human Fibroblasts into Neuronal Cells by Small Molecules

A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimer’s disease

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A novel presenilin 1 mutation (Ser169del) in a Chinese family with early-onset Alzheimer's disease

Cited by 24 publications

References 25 publications

Mutations, associated with early-onset Alzheimer&rsquo;s disease, discovered in Asian countries

Mutations, associated with early-onset Alzheimer&rsquo;s disease, discovered in Asian countries

Direct Conversion of Normal and Alzheimer’s Disease Human Fibroblasts into Neuronal Cells by Small Molecules

A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimer’s disease

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Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries