Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involv...

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Autores: Martínez-Rubio, D., Hinarejos, I., Argente-Escrig, H., Marco-Marín, C., Lozano, M.A., Gorría-Redondo, N., Lupo, V., Martí-Carrera, I., Miranda, C., Vázquez López, Esther, García-Pérez, A., Marco-Hernández, A.V., Tomás-Vila, M., Aguilera-Albesa, S., Espinós, C.
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21529
Acceso en línea:https://portalcientifico.sergas.gal//documentos/6574e34ec27a3a3585595609
http://hdl.handle.net/20.500.11940/21529
Access Level:acceso abierto
Palabra clave:Child
Humans
Genetic Heterogeneity
Mutation
Cerebellar Ataxia
Cerebellar Diseases
Ataxia
Phenotype
Spastic Paraplegia, Hereditary
Paraplegia
Neurodegenerative Diseases
Pedigree
Atrophy
Microtubule-Associated Proteins
Membrane Proteins
AS Lugo
CHULA
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oai_identifier_str oai:runa.sergas.gal:20.500.11940/21529
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repository_id_str
spelling Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar AtrophyMartínez-Rubio, D.Hinarejos, I.Argente-Escrig, H.Marco-Marín, C.Lozano, M.A.Gorría-Redondo, N.Lupo, V.Martí-Carrera, I.Miranda, C.Vázquez López, EstherGarcía-Pérez, A.Marco-Hernández, A.V.Tomás-Vila, M.Aguilera-Albesa, S.Espinós, C.ChildHumansGenetic HeterogeneityMutationCerebellar AtaxiaCerebellar DiseasesAtaxiaPhenotypeSpastic Paraplegia, HereditaryParaplegiaNeurodegenerative DiseasesPedigreeAtrophyMicrotubule-Associated ProteinsMembrane ProteinsAS LugoCHULACerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.We are in debt with the patients and their families for agreeing to participate in this study.2023info:eu-repo/semantics/articlehttps://portalcientifico.sergas.gal//documentos/6574e34ec27a3a3585595609http://hdl.handle.net/20.500.11940/21529reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/215292026-06-12T08:40:47Z
dc.title.none.fl_str_mv Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
title Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
spellingShingle Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
Martínez-Rubio, D.
Child
Humans
Genetic Heterogeneity
Mutation
Cerebellar Ataxia
Cerebellar Diseases
Ataxia
Phenotype
Spastic Paraplegia, Hereditary
Paraplegia
Neurodegenerative Diseases
Pedigree
Atrophy
Microtubule-Associated Proteins
Membrane Proteins
AS Lugo
CHULA
title_short Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
title_full Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
title_fullStr Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
title_full_unstemmed Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
title_sort Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy
dc.creator.none.fl_str_mv Martínez-Rubio, D.
Hinarejos, I.
Argente-Escrig, H.
Marco-Marín, C.
Lozano, M.A.
Gorría-Redondo, N.
Lupo, V.
Martí-Carrera, I.
Miranda, C.
Vázquez López, Esther
García-Pérez, A.
Marco-Hernández, A.V.
Tomás-Vila, M.
Aguilera-Albesa, S.
Espinós, C.
author Martínez-Rubio, D.
author_facet Martínez-Rubio, D.
Hinarejos, I.
Argente-Escrig, H.
Marco-Marín, C.
Lozano, M.A.
Gorría-Redondo, N.
Lupo, V.
Martí-Carrera, I.
Miranda, C.
Vázquez López, Esther
García-Pérez, A.
Marco-Hernández, A.V.
Tomás-Vila, M.
Aguilera-Albesa, S.
Espinós, C.
author_role author
author2 Hinarejos, I.
Argente-Escrig, H.
Marco-Marín, C.
Lozano, M.A.
Gorría-Redondo, N.
Lupo, V.
Martí-Carrera, I.
Miranda, C.
Vázquez López, Esther
García-Pérez, A.
Marco-Hernández, A.V.
Tomás-Vila, M.
Aguilera-Albesa, S.
Espinós, C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Child
Humans
Genetic Heterogeneity
Mutation
Cerebellar Ataxia
Cerebellar Diseases
Ataxia
Phenotype
Spastic Paraplegia, Hereditary
Paraplegia
Neurodegenerative Diseases
Pedigree
Atrophy
Microtubule-Associated Proteins
Membrane Proteins
AS Lugo
CHULA
topic Child
Humans
Genetic Heterogeneity
Mutation
Cerebellar Ataxia
Cerebellar Diseases
Ataxia
Phenotype
Spastic Paraplegia, Hereditary
Paraplegia
Neurodegenerative Diseases
Pedigree
Atrophy
Microtubule-Associated Proteins
Membrane Proteins
AS Lugo
CHULA
description Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://portalcientifico.sergas.gal//documentos/6574e34ec27a3a3585595609
http://hdl.handle.net/20.500.11940/21529
url https://portalcientifico.sergas.gal//documentos/6574e34ec27a3a3585595609
http://hdl.handle.net/20.500.11940/21529
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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