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Two Compound Heterozygous Variants in SNX14 Cause Stereotypies and Dystonia in Autosomal Recessive Spinocerebellar Ataxia 20

2020-09-24Journal article Open access
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dc.contributor.authorMaia, N
dc.contributor.authorSoares, Gabriela
dc.contributor.authorSilva, Cecília
dc.contributor.authorMarques, Isabel
dc.contributor.authorRodrigues, Bárbara
dc.contributor.authorSantos, Rosário
dc.contributor.authorMelo-Pires, Manuel
dc.contributor.authorde Brouwer, Arjan PM
dc.contributor.authorTemudo, Teresa
dc.contributor.authorJorge, Paula
dc.date.accessioned2021-11-23T14:50:19Z
dc.date.available2021-11-23T14:50:19Z
dc.date.issued2020-09-24
dc.description.abstractAutosomal Recessive Spinocerebellar Ataxia 20, SCAR20, is a rare condition characterized by intellectual disability, lack of speech, ataxia, coarse facies and macrocephaly, caused by SNX14 variants. While all cases described are due to homozygous variants that generally result in loss of protein, so far there are no other cases of reported compound heterozygous variants. Here we describe the first non-consanguineous SCAR20 family, the second Portuguese, with two siblings presenting similar clinical features caused by compound heterozygous SNX14 variants: NM_001350532.1:c.1195C>T, p.(Arg399*) combined with a novel complex genomic rearrangement. Quantitative PCR (Q-PCR), long-range PCR and sequencing was used to elucidate the region and mechanisms involved in the latter: two deletions, an inversion and an AG insertion: NM_001350532.1:c.[612+3028_698-2759del;698-2758_698-516inv;698-515_1171+1366delinsAG]. In silico analyses of these variants are in agreement with causality, enabling a genotype-phenotype correlation in both patients. Clinical phenotype includes dystonia and stereotypies never associated with SCAR20. Overall, this study allowed to extend the knowledge of the phenotypic and mutational spectrum of SCAR20, and to validate the role of Sorting nexin-14 in a well-defined neurodevelopmental syndrome, which can lead to cognitive impairment. We also highlight the value of an accurate clinical evaluation and deep phenotyping to disclose the molecular defect underlying highly heterogeneous condition such as intellectual disability.pt_PT
dc.description.sponsorshipUMIB was supported by National Funds through the FCT – Fundação para a Ciência e a Tecnologia (Portuguese national funding agency for science, research and technology) in the frameworks of the UID/Multi/00215/2019 project – Unit for Multidisciplinary Research in Biomedicine - UMIB/ICBAS/UP. NM and PJ were awarded with CHP grants 2017 DEFI-CHUP, E.P.E. and 2015 (145/12), respectivelypt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMaia N, Soares G, Silva C, et al. Two Compound Heterozygous Variants in SNX14 Cause Stereotypies and Dystonia in Autosomal Recessive Spinocerebellar Ataxia 20. Front Genet. 2020;11:1038. doi:10.3389/fgene.2020.01038pt_PT
dc.identifier.doi10.3389/fgene.2020.01038pt_PT
dc.identifier.issn1664-8021
dc.identifier.urihttp://hdl.handle.net/10400.16/2626
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers Research Foundationpt_PT
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fgene.2020.01038/fullpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAutosomal Recessive Spinocerebellar Ataxia 20pt_PT
dc.subjectSNX14 genept_PT
dc.subjectcerebellar hypoplasiapt_PT
dc.subjectcomplex genomic rearrangementpt_PT
dc.subjectexome sequencingpt_PT
dc.subjectintellectual disabilitypt_PT
dc.titleTwo Compound Heterozygous Variants in SNX14 Cause Stereotypies and Dystonia in Autosomal Recessive Spinocerebellar Ataxia 20pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceSwitzerlandpt_PT
oaire.citation.startPage1038pt_PT
oaire.citation.titleFrontiers in Geneticspt_PT
oaire.citation.volume11pt_PT
person.familyNameMaia
person.familyNameSantos
person.familyNameJorge
person.givenNameNuno
person.givenNameRosário
person.givenNamePaula
person.identifier1058137
person.identifier.ciencia-id4816-1492-FEB1
person.identifier.ciencia-id5717-2E67-9171
person.identifier.ciencia-idFD15-9412-CF3F
person.identifier.orcid0000-0003-3274-2474
person.identifier.orcid0000-0002-8594-6377
person.identifier.orcid0000-0002-6507-222X
person.identifier.scopus-author-id57193114189
person.identifier.scopus-author-id7201375082
person.identifier.scopus-author-id7005566496
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication58235500-e731-4550-b279-a118ae401c61
relation.isAuthorOfPublication0c5af743-da0c-4063-b8f2-ba0a859e7229
relation.isAuthorOfPublication.latestForDiscovery2d97809d-88dd-495e-99c9-82b1f674a12a

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