Clinical and Genetic Spectrum of ATP1A3 -Related Disorders
Rattachement africain : br, Mozambique, uy. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Background and ObjectivesATP1A3-related disorders comprise an expanding group of ultra-rare neurologic conditions, classically including rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome. However, accumulating reports suggest a broader and overlapping phenotypic spectrum. In this context, we established the ATP1A3 Study Group to comprehensively characterize the phenotypic and genotypic spectrum of ATP1A3-related disorders in a Brazilian cohort. MethodsWe conducted a multicenter, cross-sectional study of individuals with ATP1A3 variants. Cases were recruited across reference centers in 9 Brazilian states, with standardized extraction of demographic, genetic, neuroimaging, EEG, ECG, and clinical data. Variants were annotated using transcript NM_152296.5 (hg19). AlphaFold was used for structural visualization. Multiple correspondence analysis (MCA) was performed to explore symptom clustering. This study was approved by the Ethics Committee of Federal University of São Paulo (Approval No.: 82533124.0.0000.5505). ResultsA total of 41 patients with ATP1A3 variants were included. Seven phenotypic categories were represented: AHC (17/41), RDP (10/41), CAPOS (7/41), relapsing encephalopathy with cerebellar ataxia (RECA; 4/41), fever-induced paroxysmal weakness and encephalopathy (FIPWE; 1/41), developmental and epileptic encephalopathy 99 (DEE99; 1/41), and malformation of cortical development (MCD; 1/41). Two neonatal-onset cases (DEE99 and MCD) were fatal. We identified 22 distinct ATP1A3 variants, including 4 novel variants (p.Gln920His, p.Arg827Gly, p.Glu670Ala, and c.606+5G>T). Clinical overlap was substantial: Cognitive impairment and seizures occurred across all phenotypes; hypotonia was present in 6 of 7 main phenotypes; abnormal eye movements and fever-induced symptoms occurred in all except MCD; and paroxysmal symptoms were reported in all, except DEE99. MCA demonstrated no discrete clustering by classical phenotype, reinforcing the continuous nature of the ATP1A3 spectrum. ECG abnormalities were rare in our cohort (1/20). DiscussionOur findings expand the clinical and genetic landscape of ATP1A3-related disorders and underscore major phenotypic overlap among classical syndromes. The results highlight the need for a unified diagnostic framework. This study also demonstrates the feasibility and scientific value of coordinated rare disease research in resource-limited settings.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Clinical and Genetic Spectrum of <i>ATP1A3</i> -Related Disorders
- Date Crossref
- 01/10/2026
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Hospital Israelita Albert Einstein Department of Neurology pays non établi dans la noticeOrganisme public
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Universidade Federal de São Paulo Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Complexo Hospitalar Universitário Professor Edgard Santos pays non établi dans la noticeStructure de recherche
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Faculdade de Medicina de São José do Rio Preto pays non établi dans la noticeUniversité ou école supérieure
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Instituto Nacional de Saúde Department of Child Neurology Mozambique (code pays fourni par la source)Organisme public
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Faculdade de Medicina de Jundiaí pays non établi dans la noticeUniversité ou école supérieure
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Hospital de Clínicas de Porto Alegre Department of Medical Genetics pays non établi dans la noticeÉtablissement de santé
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Hospital de Clínicas pays non établi dans la noticeÉtablissement de santé
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Hospital Infantil Albert Sabin Department of Child Neurology pays non établi dans la noticeÉtablissement de santé
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Universidade Federal da Bahia Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Hospital Sírio-Libanês Department of Neurology pays non établi dans la noticeÉtablissement de santé
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Universidade de São Paulo Department of Neurogenetics pays non établi dans la noticeUniversité ou école supérieure
Department of Neurology — Hospital Israelita Albert Einstein, Department of Neurology — Universidade Federal de São Paulo et Complexo Hospitalar Universitário Professor Edgard Santos, avec 9 autres affiliations. Pays d’affiliation : Mozambique.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.