Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias
Abstract 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 con...
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Nature Portfolio
2021
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oai:doaj.org-article:073d2145390142cba71bb2a8e6f713c72021-11-21T12:23:19ZClinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias10.1038/s41598-021-01635-22045-2322https://doaj.org/article/073d2145390142cba71bb2a8e6f713c72021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01635-2https://doaj.org/toc/2045-2322Abstract 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.Gabriela Marchisio GiordaniFabrício DinizHelena FussigerCarelis Gonzalez-SalazarKarina Carvalho DonisFernando FreuaRoberta Paiva Magalhães OrtegaJulian Letícia de FreitasOrlando Graziani Povoas BarsottiniSergio RosembergFernando KokJosé Luiz PedrosoMarcondes Cavalcante FrançaJonas Alex Morales SauteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) |
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Medicine R Science Q Gabriela Marchisio Giordani Fabrício Diniz Helena Fussiger Carelis Gonzalez-Salazar Karina Carvalho Donis Fernando Freua Roberta Paiva Magalhães Ortega Julian Letícia de Freitas Orlando Graziani Povoas Barsottini Sergio Rosemberg Fernando Kok José Luiz Pedroso Marcondes Cavalcante França Jonas Alex Morales Saute Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias |
| description |
Abstract 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. |
| format |
article |
| author |
Gabriela Marchisio Giordani Fabrício Diniz Helena Fussiger Carelis Gonzalez-Salazar Karina Carvalho Donis Fernando Freua Roberta Paiva Magalhães Ortega Julian Letícia de Freitas Orlando Graziani Povoas Barsottini Sergio Rosemberg Fernando Kok José Luiz Pedroso Marcondes Cavalcante França Jonas Alex Morales Saute |
| author_facet |
Gabriela Marchisio Giordani Fabrício Diniz Helena Fussiger Carelis Gonzalez-Salazar Karina Carvalho Donis Fernando Freua Roberta Paiva Magalhães Ortega Julian Letícia de Freitas Orlando Graziani Povoas Barsottini Sergio Rosemberg Fernando Kok José Luiz Pedroso Marcondes Cavalcante França Jonas Alex Morales Saute |
| author_sort |
Gabriela Marchisio Giordani |
| title |
Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias |
| title_short |
Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias |
| title_full |
Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias |
| title_fullStr |
Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias |
| title_full_unstemmed |
Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias |
| title_sort |
clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/073d2145390142cba71bb2a8e6f713c7 |
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