Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Mar:75:224.e1-224.e8.
doi: 10.1016/j.neurobiolaging.2018.10.029. Epub 2018 Nov 3.

Frontotemporal dementia spectrum: first genetic screen in a Greek cohort

Eliana Marisa Ramos  1 , Christos Koros  2 , Deepika Reddy Dokuru  1 , Victoria Van Berlo  1 , Christos Kroupis  3 , Kevin Wojta  1 , Qing Wang  1 , Nikolaos Andronas  2 , Stavroula Matsi  2 , Ion N Beratis  2 , Alden Y Huang  4 , Suzee E Lee  5 , Anastasios Bonakis  2 , Chryseis Florou-Hatziyiannidou  3 , Stella Fragkiadaki  2 , Dionysia Kontaxopoulou  2 , Dimitrios Agiomyrgiannakis  6 , Vasiliki Kamtsadeli  6 , Niki Tsinia  6 , Vasiliki Papastefanopoulou  7 , Maria Stamelou  8 , Bruce L Miller  5 , Leonidas Stefanis  9 , John D Papatriantafyllou  6 , Sokratis G Papageorgiou  2 , Giovanni Coppola  10
Affiliations

Frontotemporal dementia spectrum: first genetic screen in a Greek cohort

Eliana Marisa Ramos et al. Neurobiol Aging. 2019 Mar.

Abstract

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative syndromes associated with several causative and susceptibility genes. Herein, we aimed to determine the incidence of the most common causative dementia genes in a cohort of 118 unrelated Greek FTD spectrum patients. We also screened for novel possible disease-associated variants in additional 21 genes associated with FTD or amyotrophic lateral sclerosis. Pathogenic or likely pathogenic variants were identified in 16 cases (13.6%). These included repeat expansions in C9orf72 and loss-of-function GRN variants, and likely pathogenic variants in TARDBP, MAPT, and PSEN1. We also identified 14 variants of unknown significance in other rarer FTD or amyotrophic lateral sclerosis genes that require further segregation and functional analysis. Our genetic screen revealed a high genetic burden in familial Greek FTD cases (30.4%), whereas only two of the sporadic cases (3.5%) carried a likely pathogenic variant. A substantial number of familial cases still remain without an obvious causal variant, suggesting the existence of other FTD genetic causes besides those currently screened in clinical routine.

Keywords: C9orf72; Frontotemporal dementia; GRN; Greece.

PubMed Disclaimer

Conflict of interest statement

Disclosure

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Relative frequency of pathogenic and likely pathogenic variants in a series of 118 unrelated FTD Greek cases. Eleven cases carried pathogenic variants (C9orf72 repeat expansion and loss-of-function GRN variants) while five cases carried likely pathogenic variants (MAPT, PSEN1, and TARDBP rare missense variants). Pathogenic and likely pathogenic variants were found in 30.4% of familial cases, whereas 3.5% of sporadic cases carried likely pathogenic variants. Abbreviations: ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau.
    Darwich NF, Phan JM, Kim B, Suh E, Papatriantafyllou JD, Changolkar L, Nguyen AT, O'Rourke CM, He Z, Porta S, Gibbons GS, Luk KC, Papageorgiou SG, Grossman M, Massimo L, Irwin DJ, McMillan CT, Nasrallah IM, Toro C, Aguirre GK, Van Deerlin VM, Lee EB. Darwich NF, et al. Science. 2020 Nov 20;370(6519):eaay8826. doi: 10.1126/science.aay8826. Epub 2020 Oct 1. Science. 2020. PMID: 33004675 Free PMC article.
  • C9orf72, age at onset, and ancestry help discriminate behavioral from language variants in FTLD cohorts.
    Costa B, Manzoni C, Bernal-Quiros M, Kia DA, Aguilar M, Alvarez I, Alvarez V, Andreassen O, Anfossi M, Bagnoli S, Benussi L, Bernardi L, Binetti G, Blackburn D, Boada M, Borroni B, Bowns L, Bråthen G, Bruni AC, Chiang HH, Clarimon J, Colville S, Conidi ME, Cope TE, Cruchaga C, Cupidi C, Di Battista ME, Diehl-Schmid J, Diez-Fairen M, Dols-Icardo O, Durante E, Flisar D, Frangipane F, Galimberti D, Gallo M, Gallucci M, Ghidoni R, Graff C, Grafman JH, Grossman M, Hardy J, Hernández I, Holloway GJT, Huey ED, Illán-Gala I, Karydas A, Khoshnood B, Kramberger MG, Kristiansen M, Lewis PA, Lleó A, Madhan GK, Maletta R, Maver A, Menendez-Gonzalez M, Milan G, Miller B, Mol MO, Momeni P, Moreno-Grau S, Morris CM, Nacmias B, Nilsson C, Novelli V, Öijerstedt L, Padovani A, Pal S, Panchbhaya Y, Pastor P, Peterlin B, Piaceri I, Pickering-Brown S, Pijnenburg YAL, Puca AA, Rainero I, Rendina A, Richardson AMT, Rogaeva E, Rogelj B, Rollinson S, Rossi G, Rossmeier C, Rowe JB, Rubino E, Ruiz A, Sanchez-Valle R, Sando SB, Santillo AF, Saxon J, Scarpini E, Serpente M, Smirne N, Sorbi S, Suh E, Tagliavini F, Thompson JC, Trojanowski JQ, Van Deerlin VM, Van der Zee J, Van Broeckhoven C, van Rooij J, Van Sw… See abstract for full author list ➔ Costa B, et al. Neurology. 2020 Dec 15;95(24):e3288-e3302. doi: 10.1212/WNL.0000000000010914. Epub 2020 Sep 17. Neurology. 2020. PMID: 32943482 Free PMC article.
  • Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.
    Sexton C, Solis M, Aharon-Peretz J, Alexopoulos P, Apostolova LG, Bayen E, Birkenhager B, Cappa S, Constantinidou F, Fortea J, Gerritsen DL, Hassanin HI, Ibanez A, Ioannidis P, Karageorgiou E, Korczyn A, Leroi I, Lichtwarck B, Logroscino G, Lynch C, Mecocci P, Molinuevo JL, Papatriantafyllou J, Papegeorgiou S, Politis A, Raman R, Ritchie K, Sanchez-Juan P, Sano M, Scarmeas N, Spiru L, Stathi A, Tsolaki M, Yener G, Zaganas I, Zygouris S, Carrillo M. Sexton C, et al. Alzheimers Dement. 2022 Oct;18(10):1957-1968. doi: 10.1002/alz.12588. Epub 2022 Feb 20. Alzheimers Dement. 2022. PMID: 35184367 Free PMC article. Review.
  • The Frequency of Genetic Mutations Associated With Behavioral Variant Frontotemporal Dementia in Chinese Han Patients.
    Liu L, Cui B, Chu M, Cui Y, Jing D, Li D, Xie K, Kong Y, Xia T, Wang C, Wu L. Liu L, et al. Front Aging Neurosci. 2021 Jul 8;13:699836. doi: 10.3389/fnagi.2021.699836. eCollection 2021. Front Aging Neurosci. 2021. PMID: 34305575 Free PMC article.
  • Cerebrospinal Fluid Biomarker Profile in TDP-43-Related Genetic Frontotemporal Dementia.
    Kapaki E, Boufidou F, Bourbouli M, Pyrgelis ES, Constantinides VC, Anastassopoulou C, Paraskevas GP. Kapaki E, et al. J Pers Med. 2022 Oct 21;12(10):1747. doi: 10.3390/jpm12101747. J Pers Med. 2022. PMID: 36294886 Free PMC article.
See all "Cited by" articles

References

    1. Benajiba L, Le Ber I, Camuzat A, Lacoste M, Thomas-Anterion C, Couratier P, Legallic S, Salachas F, Hannequin D, Decousus M, Lacomblez L, Guedj E, Golfier V, Camu W, Dubois B, Campion D, Meininger V, Brice A, French C, Genetic research Network on frontotemporal lobar degeneration/frontotemporal lobar degeneration with Motoneuron, D., 2009. TARDBP Mutations in Motoneuron Disease with Frontotemporal Lobar Degeneration. Ann. Neurol 65 (4), 470–473. - PubMed
    1. Benussi A, Padovani A, Borroni B, 2015. Phenotypic heterogeneity of monogenic frontotemporal dementia. Front. Aging Neurosci 7, 171. - PMC - PubMed
    1. Bernardi L, Tomaino C, Anfossi M, Gallo M, Geracitano S, Costanzo A, Colao R, Puccio G, Frangipane F, Curcio SA, Mirabelli M, Smirne N, Iapaolo D, Maletta RG, Bruni AC, 2009. Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia. Neurobiol. Aging 30, 1825–1833. - PubMed
    1. Blauwendraat C, Wilke C, Simon-Sanchez J, Jansen IE, Reifschneider A, Capell A, Haass C, Castillo-Lizardo M, Biskup S, Maetzler W, Rizzu P, Heutink P, Synofzik M, 2018. The wide genetic landscape of clinical frontotemporal dementia: systematic combined sequencing of 121 consecutive subjects. Genet. Med 20, 240–249. - PMC - PubMed
    1. Borroni B, Ferrari F, Galimberti D, Nacmias B, Barone C, Bagnoli S, Fenoglio C, Piaceri I, Archetti S, Bonvicini C, Gennarelli M, Turla M, Scarpini E, Sorbi S, Padovani A, 2014. Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol. Aging 35, 934.e7–934.e10. - PubMed

Publication types