دورية أكاديمية
A novel PSEN2 p.Ser175Phe variant in a family with Alzheimer's disease.
| العنوان: | A novel PSEN2 p.Ser175Phe variant in a family with Alzheimer's disease. |
|---|---|
| المؤلفون: | Guven G; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. zgamzee@gmail.com., Samanci B; Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Gulec C; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Hanagasi H; Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Gurvit H; Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Gokalp EE; Department of Medical Genetics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey., Tepgec F; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Guler S; Neurology Clinic, Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Sanliurfa, Turkey., Uyguner O; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Bilgic B; Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. |
| المصدر: | Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology [Neurol Sci] 2021 Jun; Vol. 42 (6), pp. 2497-2504. Date of Electronic Publication: 2021 Apr 15. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer-Verlag Italia Country of Publication: Italy NLM ID: 100959175 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1590-3478 (Electronic) Linking ISSN: 15901874 NLM ISO Abbreviation: Neurol Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Milano, Italy : Springer-Verlag Italia, c2000- |
| مواضيع طبية MeSH: | Alzheimer Disease*/genetics, Amyloid beta-Protein Precursor/genetics ; Humans ; Middle Aged ; Mutation/genetics ; Presenilin-1/genetics ; Presenilin-2/genetics |
| مستخلص: | Alzheimer's disease (AD) can be either sporadic or familial, and familial forms of AD accounts for only 5% of the cases. So far, autosomal dominantly inherited mutations in "Presenilin 1" (PSEN1), "Presenilin 2" (PSEN2), and "Amyloid precursor protein" (APP) genes were associated with familial AD. Amid the others, pathogenic mutations in the PSEN2 gene are less common. In this study, we describe a novel heterozygous PSEN2 (c.524C>T, p.Ser175Phe) alteration identified in a 58-year-old Turkish patient from a family with multiple dementia cases. This variant was further present in the patient's clinically affected maternal cousin as well as in the asymptomatic mother and two maternal aunts who were carriers of the APOE ε2/ε3 genotype. The variant is located in the conserved residue of transmembrane domain III encoded by exon 6 of the major transcript. In silico protein structure analyses predicted that this variant might change the architecture of interaction between the two alpha helixes of PSEN2. We propose that p.Ser175Phe may have a pathogenic effect on protein function and may play a significant role in the molecular pathways leading to Alzheimer's disease in this family. |
| References: | Cacace R, Sleegers K, Van Broeckhoven C (2016) Molecular genetics of early-onset Alzheimer’s disease revisited. Alzheimers Dement 12:733–748. https://doi.org/10.1016/j.jalz.2016.01.012. (PMID: 10.1016/j.jalz.2016.01.01227016693) Guerreiro RJ, Gustafson DR, Hardy J (2012) The genetic architecture of Alzheimer’s disease: beyond APP, PSENs and APOE. Neurobiol Aging 33:437–456. https://doi.org/10.1016/j.neurobiolaging.2010.03.025. (PMID: 10.1016/j.neurobiolaging.2010.03.02520594621) Park KW, An SS, Bagyinszky E, Kim S (2017) A case of possibly pathogenic PSEN2 R62C mutation in a patient with probable early-onset Alzheimer’s dementia supported by structure prediction. Clin Interv Aging 12:367–375. https://doi.org/10.2147/CIA.S128884. (PMID: 10.2147/CIA.S128884282430735315209) Binetti G, Signorini S, Squitti R, Alberici A, Benussi L, Cassetta E, Frisoni GB, Barbiero L, Feudatari E, Nicosia F, Testa C, Zanetti O, Gennarelli M, Perani D, Anchisi D, Ghidoni R, Rossini PM (2003) Atypical dementia associated with a novel presenilin-2 mutation. Ann Neurol 54:832–836. https://doi.org/10.1002/ana.10760. (PMID: 10.1002/ana.1076014681895) McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269. https://doi.org/10.1016/j.jalz.2011.03.005. (PMID: 10.1016/j.jalz.2011.03.005215142503312024) Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 4:248–249. https://doi.org/10.1038/nmeth0410-248. (PMID: 10.1038/nmeth0410-248) Schwarz JM, Cooper DN, Schuelke M, Seelow D (2014) MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 11:361–362. https://doi.org/10.1038/nmeth.2890. (PMID: 10.1038/nmeth.289024681721) Choi Y, Sims GE, Murphy S, Miller JR, Chan AP (2012) Predicting the functional effect of amino acid substitutions and indels. PLoS One 7:e46688. https://doi.org/10.1371/journal.pone.0046688. (PMID: 10.1371/journal.pone.0046688230564053466303) Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M (2019) CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 47:D886–D894. https://doi.org/10.1093/nar/gky1016. (PMID: 10.1093/nar/gky10163037182730371827) 1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR (2015) A global reference for human genetic variation. Nature 526:68–74. https://doi.org/10.1038/nature15393. (PMID: 10.1038/nature15393) Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29:308–311. https://doi.org/10.1093/nar/29.1.308. (PMID: 10.1093/nar/29.1.3081112512211125122) Guerreiro R, Sassi C, Gibbs JR, Edsall C, Hernandez D, Brown K, Lupton MK, Parkinnen L, Ansorge O, Hodges A, Ryten M, for the UK Brain Expression Consortium, Tienari PJ, Van Deerlin VM, Trojanowski JQ, Morgan K, Powell J, Singleton A, Hardy J, Bras J (2018) A comprehensive assessment of benign genetic variability for neurodegenerative disorders, bioRxiv. 270686. doi:10.1101/270686. Ashkenazy H, Abadi S, Martz E, Chay O, Mayrose I, Pupko T, Ben-Tal N (2016) ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules. Nucleic Acids Res 44:W344–W350. https://doi.org/10.1093/nar/gkw408. (PMID: 10.1093/nar/gkw408271663754987940) Piscopo P, Talarico G, Crestini A, Gasparini M, Malvezzi-Campeggi L, Piacentini E, Lenzi GL, Bruno G, Confaloni A (2010) A novel mutation in the predicted TMIII domain of the PSEN2 gene in an Italian pedigree with atypical Alzheimer’s disease. J Alzheimers Dis 20:43–47. https://doi.org/10.3233/JAD-2010-1369. (PMID: 10.3233/JAD-2010-136920164579) Guerreiro RJ, Baquero M, Blesa R, Boada M, Brás JM, Bullido MJ, Calado A, Crook R, Ferreira C, Frank A, Gómez-Isla T, Hernández I, Lleó A, Machado A, Martínez-Lage P, Masdeu J, Molina-Porcel L, Molinuevo JL, Pastor P, Pérez-Tur J, Relvas R, Oliveira CR, Ribeiro MH, Rogaeva E, Sa A, Samaranch L, Sánchez-Valle R, Santana I, Tàrraga L, Valdivieso F, Singleton A, Hardy J, Clarimón J (2010) Genetic screening of Alzheimer’s disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging 31:725–731. https://doi.org/10.1016/j.neurobiolaging.2008.06.012. (PMID: 10.1016/j.neurobiolaging.2008.06.01218667258) Wojtas A, Heggeli KA, Finch N, Baker M, Dejesus-Hernandez M, Younkin SG, Dickson DW, Graff-Radford NR, Rademakers R (2012) C9ORF72 repeat expansions and other FTD gene mutations in a clinical AD patient series from Mayo Clinic. Am J Neurodegener Dis 1:107–118. (PMID: 233833833560455) Shi Z, Wang Y, Liu S, Liu M, Liu S, Zhou Y, Wang J, Cai L, Huo YR, Gao S, Ji Y (2015) Clinical and neuroimaging characterization of Chinese dementia patients with PSEN1 and PSEN2 mutations. Dement Geriatr Cogn Disord 39:32–40. https://doi.org/10.1159/000366272. (PMID: 10.1159/00036627225323700) Wang JC, Alinaghi S, Tafakhori A, Sikora E, Azcona LJ, Karkheiran S, Goate A, Paisán-Ruiz C, Darvish H (2018) Genetic screening in two Iranian families with early-onset Alzheimer’s disease identified a novel PSEN1 mutation, Neurobiol Aging. 62 244.e15-244.e17. doi: 10.1016/j.neurobiolaging.2017.10.011. Taddei K, Kwok JB, Kril JJ, Halliday GM, Creasey H, Hallupp M, Fisher C, Brooks WS, Chung C, Andrews C, Masters CL, Schofield PR, Martins RN (1998) Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer’s disease. Neuroreport 9:3335–3339. https://doi.org/10.1097/00001756-199810050-00034. (PMID: 10.1097/00001756-199810050-000349831473) Ezquerra M, Carnero C, Blesa R, Gelpí JL, Ballesta F, Oliva R (1999) A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures. Neurology. 52:566–570. https://doi.org/10.1212/wnl.52.3.566. (PMID: 10.1212/wnl.52.3.56610025789) Guo J, Wei J, Liao S, Wang L, Jiang H, Tang B (2010) A novel presenilin 1 mutation (Ser169del) in a Chinese family with early-onset Alzheimer's disease. Neurosci Lett 468:34–37. https://doi.org/10.1016/j.neulet.2009.10.055. (PMID: 10.1016/j.neulet.2009.10.05519853643) Giau VV, Pyun JM, Bagyinszky E, An SSA, Kim S (2018) A pathogenic PSEN2 p.His169Asn mutation associated with early-onset Alzheimer’s disease. Clin Interv Aging 13:1321–1329. https://doi.org/10.2147/CIA.S170374. (PMID: 10.2147/CIA.S170374301048666074827) Xia M, Chen S, Shi Y, Huang Y, Xu J, Zhao T, He S, Wu Y, Xu C, Zang W, J. Zhang (2015) Probable novel PSEN2 Pro123Leu mutation in a Chinese Han family of Alzheimer’s disease, Neurobiol Aging. 36, 3334.e13-3334.e18. doi: 10.1016/j.neurobiolaging.2015.09.003. Vélez JI, Lopera F, Sepulveda-Falla D, Patel HR, Johar AS, Chuah A, Tobón C, Rivera D, Villegas A, Cai Y, Peng K, Arkell R, Castellanos FX, Andrews SJ, Silva Lara MF, Creagh PK, Easteal S, de Leon J, Wong ML, Licinio J, Mastronardi CA, Arcos-Burgos M (2016) APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer's disease. Mol Psychiatry 21:916–924. https://doi.org/10.1038/mp.2015.177. (PMID: 10.1038/mp.2015.17726619808) Arboleda-Velasquez JF, Lopera F, O'Hare M, Delgado-Tirado S, Marino C, Chmielewska N, Saez-Torres KL, Amarnani D, Schultz AP, Sperling RA, Leyton-Cifuentes D, Chen K, Baena A, Aguillon D, Rios-Romenets S, Giraldo M, Guzmán-Vélez E, Norton DJ, Pardilla-Delgado E, Artola A, Sanchez JS, Acosta-Uribe J, Lalli M, Kosik KS, Huentelman MJ, Zetterberg H, Blennow K, Reiman RA, Luo J, Chen Y, Thiyyagura P, Su Y, Jun GR, Naymik M, Gai X, Bootwalla M, Ji J, Shen L, Miller JB, Kim LA, Tariot PN, Johnson KA, Reiman EM, Quiroz YT (2019) Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. Nat Med 25:1680–1683. https://doi.org/10.1038/s41591-019-0611-3. (PMID: 10.1038/s41591-019-0611-3316860346898984) Sherrington R, Froelich S, Sorbi S, Campion D, Chi H, Rogaeva EA, Levesque G, Rogaev EL, Lin C, Liang Y, Ikeda M, Mar L, Brice A, Agid Y, Percy ME, Clerget-Darpoux F, Piacentini S, Marcon G, Nacmias B, Amaducci L, Frebourg T, Lannfelt L, Rommens JM, St George-Hyslop PH (1996) Alzheimer’s disease associated with mutations in presenilin 2 is rare and variably penetrant. Hum Mol Genet 5:985–988. https://doi.org/10.1093/hmg/5.7.985. (PMID: 10.1093/hmg/5.7.9858817335) Finckh U, Muller-Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G, Alberici A, Hock C, Nitsch RM, Gal A (2000) High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet 66:110–117. https://doi.org/10.1086/302702. (PMID: 10.1086/30270210631141) Ezquerra M, Lleó A, Castellví M, Queralt R, Santacruz P, Pastor P, Molinuevo JL, Blesa R, Oliva R (2003) A novel mutation in the PSEN2 gene (T430M) associated with variable expression in a family with early-onset Alzheimer disease. Arch Neurol 60(8):1149–1151. https://doi.org/10.1001/archneur.60.8.1149. (PMID: 10.1001/archneur.60.8.114912925374) Lalli MA, Bettcher BM, Arcila ML, Garcia G, Guzman C, Madrigal L, Ramirez L, Acosta-Uribe J, Baena A, Wojta KJ, Coppola G, Fitch R, de Both MD, Huentelman MJ, Reiman EM, Brunkow ME, Glusman G, Roach JC, Kao AW, Lopera F, Kosik KS (2015) Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer’s disease. Mol Psychiatry 20(11):1294–1300. https://doi.org/10.1038/mp.2015.131. (PMID: 10.1038/mp.2015.131263241034759097) Piaceri I, Chiari A, Galli C, Bagnoli S, Ferrari C, Trujillo Saavedra S, Molinari MA, Vinceti G, Sorbi S, Nacmias B (2020) Incomplete penetrance in familial Alzheimer’s disease with PSEN1 Ala260Gly mutation. Neurol Sci 41(8):2263–2266. https://doi.org/10.1007/s10072-020-04421-6. (PMID: 10.1007/s10072-020-04421-632328830) |
| فهرسة مساهمة: | Keywords: Alzheimer’s disease; PSEN2; S175F; novel |
| المشرفين على المادة: | 0 (Amyloid beta-Protein Precursor) 0 (PSEN2 protein, human) 0 (Presenilin-1) 0 (Presenilin-2) |
| تواريخ الأحداث: | Date Created: 20210415 Date Completed: 20210531 Latest Revision: 20210531 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1007/s10072-021-05243-w |
| PMID: | 33855622 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1590-3478 |
|---|---|
| DOI: | 10.1007/s10072-021-05243-w |