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Mutations in presenilin 2 and its implications in Alzheimer's disease and other dementia-associated disorders.

Cai Y, An SS, Kim S - Clin Interv Aging (2015)

Bottom Line: Only two were found in Korean populations.Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia.Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Gyeonggi-do, South Korea.

ABSTRACT
Alzheimer's disease (AD) is the most common form of dementia. Mutations in the genes encoding presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein have been identified as the main genetic causes of familial AD. To date, more than 200 mutations have been described worldwide in PSEN1, which is highly homologous with PSEN2, while mutations in PSEN2 have been rarely reported. We performed a systematic review of studies describing the mutations identified in PSEN2. Most PSEN2 mutations were detected in European and in African populations. Only two were found in Korean populations. Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia. Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

No MeSH data available.


Related in: MedlinePlus

Missense mutations in PSEN2 and their pathogenicity.Abbreviations: SNP, single nucleotide polymorphism; EX, exon.
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f2-cia-10-1163: Missense mutations in PSEN2 and their pathogenicity.Abbreviations: SNP, single nucleotide polymorphism; EX, exon.

Mentions: Mutations in the presenilin genes are the main causes of familial EOAD. Similar to APP, mutant presenilins can enhance Aβ production and contribute to AD development, whereas PSEN2 plays less of a role than PSEN1. An extensive literature search for mutations in PSEN2 was conducted. As of date, 38 mutations have been reported. The number of mutations identified in PSEN1 is greater than five times this number.31 Two PSEN2 mutations, Glu126fs and Lys306fs, are frameshift mutations, and the others are nonsynonymous substitutions (Table 1). PSEN2 mutations are associated with variable penetrance and a wide range in the age of disease onset, from 45 to 88.32,33PSEN2 mutations are associated with both EOAD and LOAD. Only 17 of the 38 are predicted to be disease-causing mutations (Figure 2). Ten of the mutations are not pathogenic and the others are still unclear. Sixteen mutations are located within transmembrane domains. Cell-based studies suggest that four of these mutations, T122P, N141I, M239I, and M239V, cause an increase in the amount of Aβ peptide.34 The mutations T122R, S130L, and M239I were found to alter calcium signaling.35–37 Most of these mutations were discovered in European and African populations. Until now, only four missense mutations were described in Asian populations: Asn141Tyr was associated with EOAD in a Chinese Han family;37 Gly34Ser was found in a Japanese patient;39 and Arg62Cys and Val214Leu were described in the Korean patients.6


Mutations in presenilin 2 and its implications in Alzheimer's disease and other dementia-associated disorders.

Cai Y, An SS, Kim S - Clin Interv Aging (2015)

Missense mutations in PSEN2 and their pathogenicity.Abbreviations: SNP, single nucleotide polymorphism; EX, exon.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507455&req=5

f2-cia-10-1163: Missense mutations in PSEN2 and their pathogenicity.Abbreviations: SNP, single nucleotide polymorphism; EX, exon.
Mentions: Mutations in the presenilin genes are the main causes of familial EOAD. Similar to APP, mutant presenilins can enhance Aβ production and contribute to AD development, whereas PSEN2 plays less of a role than PSEN1. An extensive literature search for mutations in PSEN2 was conducted. As of date, 38 mutations have been reported. The number of mutations identified in PSEN1 is greater than five times this number.31 Two PSEN2 mutations, Glu126fs and Lys306fs, are frameshift mutations, and the others are nonsynonymous substitutions (Table 1). PSEN2 mutations are associated with variable penetrance and a wide range in the age of disease onset, from 45 to 88.32,33PSEN2 mutations are associated with both EOAD and LOAD. Only 17 of the 38 are predicted to be disease-causing mutations (Figure 2). Ten of the mutations are not pathogenic and the others are still unclear. Sixteen mutations are located within transmembrane domains. Cell-based studies suggest that four of these mutations, T122P, N141I, M239I, and M239V, cause an increase in the amount of Aβ peptide.34 The mutations T122R, S130L, and M239I were found to alter calcium signaling.35–37 Most of these mutations were discovered in European and African populations. Until now, only four missense mutations were described in Asian populations: Asn141Tyr was associated with EOAD in a Chinese Han family;37 Gly34Ser was found in a Japanese patient;39 and Arg62Cys and Val214Leu were described in the Korean patients.6

Bottom Line: Only two were found in Korean populations.Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia.Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Gyeonggi-do, South Korea.

ABSTRACT
Alzheimer's disease (AD) is the most common form of dementia. Mutations in the genes encoding presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein have been identified as the main genetic causes of familial AD. To date, more than 200 mutations have been described worldwide in PSEN1, which is highly homologous with PSEN2, while mutations in PSEN2 have been rarely reported. We performed a systematic review of studies describing the mutations identified in PSEN2. Most PSEN2 mutations were detected in European and in African populations. Only two were found in Korean populations. Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia. Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

No MeSH data available.


Related in: MedlinePlus