%0 Journal Article
%A Lopriore, Piervito
%A Ünlütürk, Zeynep
%A Klopstock, Thomas
%A Karaa, Amel
%A Rouzier, Cecile
%A Domínguez-González, Cristina
%A Lamperti, Costanza
%A Mancuso, Michelangelo
%A Cecchi, Giulia
%A Montano, Vincenzo
%A Siciliano, Gabriele
%A Nicoletta, Valeria
%A Maioli, Mariantonietta
%A Primiano, Guido
%A Servidei, Serenella
%A La Morgia, Chiara
%A Carelli, Valerio
%A Valentino, Maria Lucia
%A Caporali, Leonardo
%A Arena, Ignazio Giuseppe
%A Musumeci, Olimpia
%A Lopergolo, Diego
%A Malandrini, Alessandro
%A Gallus, Gian Nicola
%A Filosto, Massimiliano
%A Bello, Luca
%A Pegoraro, Elena
%A Comi, Giacomo Pietro
%A Magri, Francesca
%A Ronchi, Dario
%A Di Fonzo, Alessio
%A Percetti, Marco
%A Azzimonti, Matteo
%A Büchner, Boriana
%A Prokisch, Holger
%A Bermejo-Guerrero, Laura
%A Procaccio, Vincent
%A Gaignard, Pauline
%A Echaniz-Laguna, Andoni
%A Schiff, Manuel
%A Rötig, Agnès
%A Toutain, Annick
%A Paquis-Flucklinger, Véronique
%A Morel, Godelieve
%A Robin, Stéphanie
%A Nadaj-Pakleza, Aleksandra
%A Chanson, Jean-Baptiste
%A Chaussenot, Annabelle
%A Ait-El-Mkadem Saadi, Samira
%A Trimouille, Aurélien
%A Tranchant, Christine
%A Salort-Campana, Emmanuelle
%A Bieth, Eric
%A Sacconi, Sabrina
%A Duval, Fanny
%A Restrepo Vera, Juan Luis
%A Molnar, Maria Judit
%A Vissing, John
%A Haas, Richard
%A Larson, Austin
%A Enns, Gregory M
%A Parikh, Sumit
%A Goldstein, Amy
%A Hirano, Michio
%T Clinical and Genotypic Spectrum of Twinkle-Related Disorders: Insights From a Multinational Cohort Study.
%J Neurology
%V 106
%N 3
%@ 0028-3878
%C Philadelphia, Pa.
%I Wolters Kluwer
%M DZNE-2026-00074
%P e214401
%D 2026
%X Twinkle, encoded by the TWNK gene, is a mitochondrial DNA helicase that unwinds the double helix of DNA during replication, playing a pivotal role in mitochondrial function. Twinkle-related disorders encompass a variety of genetic disorders characterized by mitochondrial dysfunction. Although several phenotypes have been described, the full clinical and molecular spectrum remains poorly defined. The aim of this study was to characterize the phenotypic and genotypic variability among multinational patients diagnosed with Twinkle-related disorders.A retrospective cohort study was conducted in patients with Twinkle-related disorders at several specialized centers in Italy, France, Germany, Spain, Denmark, Hungary, and the United States, establishing the Twinkle-Related Disorders International Consortium for Trial Readiness (TReDIC). Data were collected from medical records, including clinical features, age at onset, disease progression, and results from genetic testing. Phenotypic categories included infantile-onset cerebellar ataxia, parkinsonism, primary mitochondrial myopathy (PMM), multisystem involvement, asymptomatic carriers, undetermined phenotypes, and other phenotypes. All patients' diagnoses were confirmed by genetic analysis, and their genetic variants were noted. Outcomes included prevalence of phenotypes, symptom chronology, and mutational patterns.The study included a total of 189 patients (116 female), with a mean age at symptom onset of 40.3 years. At the time of analysis, 70.4
%K Humans
%K Female
%K Male
%K Adult
%K Middle Aged
%K Retrospective Studies
%K Adolescent
%K Child
%K Phenotype
%K Genotype
%K Young Adult
%K Mitochondrial Diseases: genetics
%K Mitochondrial Diseases: physiopathology
%K Cohort Studies
%K Mitochondrial Proteins: genetics
%K Aged
%K Child, Preschool
%K Mutation
%K Age of Onset
%K Mitochondrial Myopathies: genetics
%K DNA Helicases
%K TWNK protein, human (NLM Chemicals)
%K Mitochondrial Proteins (NLM Chemicals)
%K DNA Helicases (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41538773
%R 10.1212/WNL.0000000000214401
%U https://pub.dzne.de/record/284031