Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias

• Autor(a) principal: Giordani, Gabriela Marchisio
• Data de Publicação: 2021
• Outros Autores: Lima, Fabricio Diniz de, Fussiger, Helena, González Salazar, Carelis Del Valle, Donis, Karina Carvalho, Freua, Fernando, Ortega, Roberta Paiva Magalhões, Freitas, Julian Letícia de, Barsottini, Orlando Graziani Povoas, Rosemberg, Sergio, Kok, Fernando, Pedroso, José Luiz, França Júnior, Marcondes Cavalcante, Saute, Jonas Alex Morales
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/250494
• topic: Predisposição genética para doença; Paraplegia espástica hereditária; Vigilância da população

The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). A multicenter historical cohort was performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset < 12 years-old) were reviewed from 2011 to 2020. One hundred and six individuals (83 families) with suspicion of childhood-onset HSP were evaluated, being 68 (50 families) with solved genetic diagnosis, 6 (5 families) with candidate variants in HSP-related genes and 32 (28 families) with unsolved genetic diagnosis. The most common childhood-onset subtype was SPG4, 11/50 (22%) families with solved genetic diagnosis; followed by SPG3A, 8/50 (16%). Missense pathogenic variants in SPAST were found in 54.5% of probands, favoring the association of this type of variant to childhood-onset SPG4. Survival curves to major handicap and cross-sectional Spastic Paraplegia Rating Scale progressions confirmed the slow neurological deterioration in SPG4 and SPG3A. Most common complicating features and twenty variants not previously described in HSP-related genes were reported. These results are fundamental to understand the molecular and clinical epidemiology of childhood-onset HSP, which might help on differential diagnosis, patient care and guiding future collaborative trials for these rare diseases.