TY  - JOUR
AU  - Lopriore, Piervito
AU  - Ünlütürk, Zeynep
AU  - Klopstock, Thomas
AU  - Karaa, Amel
AU  - Rouzier, Cecile
AU  - Domínguez-González, Cristina
AU  - Lamperti, Costanza
AU  - Mancuso, Michelangelo
AU  - Cecchi, Giulia
AU  - Montano, Vincenzo
AU  - Siciliano, Gabriele
AU  - Nicoletta, Valeria
AU  - Maioli, Mariantonietta
AU  - Primiano, Guido
AU  - Servidei, Serenella
AU  - La Morgia, Chiara
AU  - Carelli, Valerio
AU  - Valentino, Maria Lucia
AU  - Caporali, Leonardo
AU  - Arena, Ignazio Giuseppe
AU  - Musumeci, Olimpia
AU  - Lopergolo, Diego
AU  - Malandrini, Alessandro
AU  - Gallus, Gian Nicola
AU  - Filosto, Massimiliano
AU  - Bello, Luca
AU  - Pegoraro, Elena
AU  - Comi, Giacomo Pietro
AU  - Magri, Francesca
AU  - Ronchi, Dario
AU  - Di Fonzo, Alessio
AU  - Percetti, Marco
AU  - Azzimonti, Matteo
AU  - Büchner, Boriana
AU  - Prokisch, Holger
AU  - Bermejo-Guerrero, Laura
AU  - Procaccio, Vincent
AU  - Gaignard, Pauline
AU  - Echaniz-Laguna, Andoni
AU  - Schiff, Manuel
AU  - Rötig, Agnès
AU  - Toutain, Annick
AU  - Paquis-Flucklinger, Véronique
AU  - Morel, Godelieve
AU  - Robin, Stéphanie
AU  - Nadaj-Pakleza, Aleksandra
AU  - Chanson, Jean-Baptiste
AU  - Chaussenot, Annabelle
AU  - Ait-El-Mkadem Saadi, Samira
AU  - Trimouille, Aurélien
AU  - Tranchant, Christine
AU  - Salort-Campana, Emmanuelle
AU  - Bieth, Eric
AU  - Sacconi, Sabrina
AU  - Duval, Fanny
AU  - Restrepo Vera, Juan Luis
AU  - Molnar, Maria Judit
AU  - Vissing, John
AU  - Haas, Richard
AU  - Larson, Austin
AU  - Enns, Gregory M
AU  - Parikh, Sumit
AU  - Goldstein, Amy
AU  - Hirano, Michio
TI  - Clinical and Genotypic Spectrum of Twinkle-Related Disorders: Insights From a Multinational Cohort Study.
JO  - Neurology
VL  - 106
IS  - 3
SN  - 0028-3878
CY  - Philadelphia, Pa.
PB  - Wolters Kluwer
M1  - DZNE-2026-00074
SP  - e214401
PY  - 2026
AB  - 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
KW  - Humans
KW  - Female
KW  - Male
KW  - Adult
KW  - Middle Aged
KW  - Retrospective Studies
KW  - Adolescent
KW  - Child
KW  - Phenotype
KW  - Genotype
KW  - Young Adult
KW  - Mitochondrial Diseases: genetics
KW  - Mitochondrial Diseases: physiopathology
KW  - Cohort Studies
KW  - Mitochondrial Proteins: genetics
KW  - Aged
KW  - Child, Preschool
KW  - Mutation
KW  - Age of Onset
KW  - Mitochondrial Myopathies: genetics
KW  - DNA Helicases
KW  - TWNK protein, human (NLM Chemicals)
KW  - Mitochondrial Proteins (NLM Chemicals)
KW  - DNA Helicases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41538773
DO  - DOI:10.1212/WNL.0000000000214401
UR  - https://pub.dzne.de/record/284031
ER  -