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Nature genetics · 2026

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

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

Аннотация

Atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions (aFTLD-U) is neuropathologically characterized by aggregation of the FET family of proteins and clinically manifests as sporadic young-onset frontotemporal dementia. Here we describe a major risk locus on chr15q14 identified through a genome-wide association study in 59 pathologically confirmed aFTLD-U cases and 3,153 controls (lead single nucleotide polymorphism rs549846383, P = 5.85 × 10-21, odds ratio 26.7). When combined with data from 28 additional aFTLD-U cases, 3,712 controls and 3,215 individuals with other neurodegenerative diseases and by leveraging in-house and public long-read genome sequencing data from 1,715 individuals, we identified a tandem repeat expansion on the associated haplotypes in an intron of GOLGA8A. We found variation in repeat length, motif length, and motif sequence, with long CT-dimer expansions strongly associated with aFTLD-U. Although the functional consequence of this repeat remains unknown, its presence in nearly 60% of aFTLD-U cases points to a fundamental role in disease pathogenesis.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты