Telethon Undiagnosed Disease Program: Structured approach to solving rare childhood-onset genetic diseases.
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.
Torella Annalaura, Morleo Manuela, Spampanato Carmine, Castello Raffaele, Zanobio Mariateresa, Piluso Giulio, Di Letto Pasquale, Onore Maria Elena, Rahman Sarah Iffat, Musacchia Francesco, Pinelli Michele, Vitiello Giuseppina, De Riso Giulia, Selicorni Angelo, Mariani Milena, Daolio Cecilia, Capra Valeria, Scala Marcello, Nardecchia Francesca, Galosi Serena, Mastrangelo Mario, Manti Filippo, Milani Donatella, Romano Corrado, Greco Donatella, Ciaccio Claudia, D'Arrigo Stefano, De Laurentiis Arianna, Coppola Antonietta, Zollino Marcella, Pasquetti Domizia, L'Erario Federica Francesca, Tummolo Albina, Santoro Claudia, Garavelli Livia, Marini Carla, Bigoni Stefania, Tirozzi Alfonsina, Cetrangolo Viviana, Parenti Giancarlo, Di Bernardo Diego, Peron Angela, Maitz Silvia, Accogli Andrea, Cappuccio Gerarda, Banfi Sandro, Casari Giorgio, Ballabio Andrea, Brunetti-Pierri Nicola, Nigro Vincenzo, Telethon Undiagnosed Disease Study group
Аннотация
METHODS: Launched in 2016, the Telethon Undiagnosed Diseases Program provides a structured, multicenter approach to rare disease diagnosis. Standardized case submission criteria ensured consistent clinical data collection. Children with severe, multisystemic disorders and prior negative genetic tests were eligible. After case approval, trio-based exome sequencing was performed, with regular reanalysis for unsolved cases until December 2024.
RESULTS: Between June 2016 and December 2023, 1338 cases were submitted by 60 clinicians from 22 Italian centers; 1019 were accepted. A definitive genetic diagnosis was achieved in 49% of cases, implicating 330 genes. Most pathogenic variants (70.2%) were de novo, reflecting demographic trends, such as delayed parenthood. The remainder included autosomal recessive or X-linked variants, with homozygosity observed in 9% of patients.
CONCLUSION: The Telethon Undiagnosed Diseases Program significantly shortened the average diagnostic odyssey of ∼8 years. Children born after 2016 benefited from faster diagnoses. This initiative offers a scalable, cost-effective model for improving diagnosis, guiding treatment, and supporting therapeutic innovation in rare pediatric diseases.