Expanding the Genetic and Phenotypic Spectrum of DYT-VPS16: The Importance of Splice-Site Variants.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Westenberger Ana, Verdura Edgard, Radefeldt Mandy, Sanderson Leslie E, Tripolszki Kornelia, Marcé-Grau Anna, Cazurro-Gutiérrez Ana, Nikoncuk Anita, Herzog Rebecca, Al-Ali Ruslan, Ferreira Mariana, Almeida Ligia S, Silveira Tainá Regina Damaceno, Khan Suliman, Maia Raphael Doyle, Klivényi Péter, Salamon András, Baltaci Volkan, Subasioglu Asli, Prada-Arismendy Jeanette, Čuturilo Goran, Loens Sebastian, Tadic Vera, Maystadt Isabelle, Karadurmus Deniz, Leube Barbara, De Winter Jonathan, Monticelli Alice, De Waele Liesbeth, Baets Jonathan, Vinkšel Mateja, Maver Aleš, Tschopp Lorena, Ziegler Gabriela, Sanguinetti Ana, Lohmann Katja, Barakat Tahsin Stefan, Bauer Peter, Perez-Dueñas Belén, Bertoli-Avella Aida M
Аннотация
METHODS: We explored the clinical and genotypic spectrum of DYT-VPS16 by investigating early-onset dystonia patients with VPS16 variants discovered in our large Biodatabank and through gene-matching initiatives. Patient samples were analyzed by exome/Sanger and RNA/cDNA sequencing.
RESULTS: We identified 16 previously unreported DYT-VPS16 patients (7 male, median age at onset [AAO]: 12 years). Patients with initial leg involvement had an AAO more than 10 years earlier than those with involvement of the arms/craniocervical region. Dystonia progressed in 95%, generalized in 50%, and was accompanied by pyramidal, cerebellar, or psychiatric features in 25% of patients. Two young individuals benefited greatly from timely deep brain stimulation (DBS) surgery. Of the 11 identified VPS16 variants, 10 were novel. Utilizing RNA-Seq or cDNA sequencing, we discovered alternatively spliced transcripts, thereby elucidating the effects of splice-site, near-splice-site, and exonic variants.
CONCLUSIONS: We expand the phenotypic and mutational spectrum of DYT-VPS16, emphasize the utility of RNA-Seq in clarifying VPS16 variant pathogenicity, and advocate for timely DBS as a promising therapeutic option for DYT-VPS16 patients. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.