aFTLD-U GOLGA8A

A rare subtype of Frontotemporal Lobar Degeneration with FET protein inclusions (FTLD-FET). Categorized clinically by behavioral variant frontotemporal dementia (bvFTD) with TAF15/FUS/EWSR1 positive inclusions. Associated with psychiatric symptoms and frontal/striatal atrophy¹.

Prevalence

FTLD-FET makes up ~5–10% of FTLD, and aFTLD-U is the most common FTLD-FET subtype. Prevalence estimates are challenging because diagnosis typically requires neuropathology at autopsy. Risk haplotypes are enriched in Amish and non-Finnish europeans.¹.

Age of Onset Details

Typical: 34-55; Range: 21-72¹.

Locus

hg19

chr15:34711626-34711652

hg38

chr15:34419425-34419451

t2t

chr15:32225152-32225178

Details

Variation in repeat length, motif length, and motif sequence, with long CT-dimer expansions strongly associated with aFTLD-U risk. CCTT and CCCTCT motif expansions have been observed in unaffected individuals. CCCCT repeats were present in one aFTLD-U case. Proposed risk-associated expansions are typically >450 bp with >80% CT content and/or contain >190 CT dimers, though unaffected carriers have also been observed. Although the functional consequence of this repeat remains unknown, its presence in nearly 60% of aFTLD-U cases points to a major role in disease pathogenesis¹.

Mechanism

Unknown [@pmid:41820575].

Year

2026¹

Gene Strand

Alleles

Ref. Motif

TTTC

Benign (ref.)

CCTT, CCCTCT

Benign (gene)

AAGG, AGAGGG

Pathogenic (ref.)

Pathogenic (gene)

Unknown (ref.)

CCCCT

Unknown (gene)

AGGGG

References

Direct supporting references for info on this page.

A repeat expansion in GOLGA8A is a major risk factor for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.

Wouter,De Coster, Marleen,Van den Broeck, Matt,Baker, Nikhil B,Ghayal, Sarah,Wynants, Anthony,Batzler, Cyril,Pottier, Sara,Alidadiani, Fahri,Küçükali, Gregory D,Jenkins, Rafaela,Policarpo, Marka,van Blitterswijk, Mariely,DeJesus-Hernandez, Alexandra I,Soto-Beasley, Júlia,Faura, Elise,Coopman, Saskia,Hutten, Merel O,Mol, David,Wallon, Anne,Sieben, Elizabeth C,Finger, Melissa E,Murray, Shelley L,Forrest, Maria C,Tartaglia, Claire,Troakes, Jeroen G J,van Rooij, Aivi T,Nguyen, R Ross,Reichard, Natalie L,Woodman, Alissa L,Nana, Sandra,Weintraub, Tamar,Gefen, Bart,De Vil, Istvan,Bodi, Oscar L,Lopez, Susana,Boluda, Serge,Belliard, Florence,Lebert, Florent,Marguet, Qinwen,Mao, Marsel M,Mesulam, Adam L,Boxer, Mathieu,Vandenbulcke, EunRan,Suh, Jolien,Schaeverbeke, Jean-Charles,Lambert, Sonja W,Scholz, Clifton L,Dalgard, Bryan J,Traynor, Raphael J,Gibbs, Gerard D,Schellenberg, Dorothee,Dormann, Geert,Joris, Tim,De Pooter, Peter,De Rijk, Svenn,D'Hert, Jasper,Van Dongen, Julie,van der Zee, Mojca,Strazisar, Marla,Gearing, Thomas,Kukar, Margaret,Flanagan, Sebastiaan,Engelborghs, Bernardino,Ghetti, Kathy L,Newell, Andrew,King, Sigrun,Roeber, Howard J,Rosen, Salvatore,Spina, Patrick,Cras, Nilüfer,Ertekin-Taner, Zbigniew K,Wszolek, Ryan J,Uitti, William P,Cheshire, Wolfgang,Singer, Jochen,Herms, Keith A,Josephs, Jennifer L,Whitwell, Ronald C,Petersen, Florence,Pasquier, Gaël,Nicolas, Rudolph,Castellani, Jonathan,Glass, Bruce L,Miller, Gabor G,Kovacs, Robert A,Rissman, Annie,Hiniker, Vincent,Deramecourt, Lee-Cyn,Ang, Jin,Lee-Way, Vivianna M,Van Deerlin, Brittany N,Dugger, Dietmar R,Thal, Lea T,Grinberg, Carlos,Cruchaga, Thomas,Arzberger, David G,Munoz, Julia,Keith, Lorne,Zinman, Ekaterina,Rogaeva, Edward B,Lee, Stephen J,Haggarty, Olaf,Ansorge, Masud,Husain, Glenda M,Halliday, Safa,Al-Sarraj, Owen A,Ross, Kristel,Sleegers, Rik,Vandenberghe, Bradley F,Boeve, Neill R,Graff-Radford, Julia,Kofler, Charles L,White, Tammaryn,Lashley, Manuela,Neumann, Joanna M,Biernacka, William W,Seeley, Harro,Seelaar, John C,van Swieten, Jonathan D,Rohrer, Dennis W,Dickson, Ian R A,Mackenzie, Rosa,Rademakers

Nature genetics · 2026-03-12

pmid:41820575