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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-01635-2 |
| _version_ | 1818928922476150784 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T03:36:36Z |
| format | Article |
| id | doaj.art-073d2145390142cba71bb2a8e6f713c7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T03:36:36Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-073d2145390142cba71bb2a8e6f713c72022-12-21T19:54:51ZengNature PortfolioScientific Reports2045-23222021-11-011111910.1038/s41598-021-01635-2Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegiasGabriela Marchisio Giordani0Fabrício Diniz1Helena Fussiger2Carelis Gonzalez-Salazar3Karina Carvalho Donis4Fernando Freua5Roberta Paiva Magalhães Ortega6Julian Letícia de Freitas7Orlando Graziani Povoas Barsottini8Sergio Rosemberg9Fernando Kok10José Luiz Pedroso11Marcondes Cavalcante França12Jonas Alex Morales Saute13Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do SulGraduate Program in Medical Physiopathology, Universidade Estadual de Campinas (UNICAMP)Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do SulGraduate Program in Medical Physiopathology, Universidade Estadual de Campinas (UNICAMP)Neurogenetics, Clinical Research Center, Hospital de Clínicas de Porto Alegre (HCPA)Departamento de Neurologia, Hospital das Clínicas, Universidade de São PauloIrmandade da Santa Casa de Misericórdia de São PauloDepartment of Neurology, Ataxia Unit Universidade Federal de São PauloDepartment of Neurology, Ataxia Unit Universidade Federal de São PauloIrmandade da Santa Casa de Misericórdia de São PauloDepartamento de Neurologia, Hospital das Clínicas, Universidade de São PauloDepartment of Neurology, Ataxia Unit Universidade Federal de São PauloGraduate Program in Medical Physiopathology, Universidade Estadual de Campinas (UNICAMP)Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do SulAbstract 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.https://doi.org/10.1038/s41598-021-01635-2 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-01635-2 |
| work_keys_str_mv | AT gabrielamarchisiogiordani clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT fabriciodiniz clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT helenafussiger clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT carelisgonzalezsalazar clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT karinacarvalhodonis clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT fernandofreua clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT robertapaivamagalhaesortega clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT julianleticiadefreitas clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT orlandograzianipovoasbarsottini clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT sergiorosemberg clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT fernandokok clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT joseluizpedroso clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT marcondescavalcantefranca clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias AT jonasalexmoralessaute clinicalandmolecularcharacterizationofalargecohortofchildhoodonsethereditaryspasticparaplegias |