Título:
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New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32
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Autor/a:
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Serrano Munuera, Carmen; Corral Juan, Marc; Stevanin, Giovanni; San Nicolás, Hector; Roig, Carles; Corral, Jordi; Campos, Berta; Jorge, Laura de; Morcillo Suárez, Carlos, 1969-; Navarro i Cuartiellas, Arcadi, 1969-; Forlani, Sylvie; Durr, Alexandra; Kulisevsky, Jaime J.; Brice, Alexis; Sánchez, Ivelisse; Volpini, Victor; Matilla Dueñas, Antoni
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Abstract:
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IMPORTANCE: To provide clinical and genetic diagnoses for patients' conditions, it is important to identify and characterize the different subtypes of spinocerebellar ataxia (SCA). OBJECTIVE: To clinically and genetically characterize a Spanish kindred with pure SCA presenting with altered vertical eye movements. DESIGN Family study of ambulatory patients. Electro-oculographic and genetics studies were performed in 2 referral university centers. SETTING: Primary care institutional center in Spain. PARTICIPANTS: Thirty-six participants from a large Spanish kindred were clinically examined, and 33 family members were genetically examined. Detailed clinical data were obtained from 9 affected relatives. Two ataxic siblings and 2 asymptomatic family members were examined using an enhanced clinical protocol for a follow-up period of 7 years. MAIN OUTCOMES AND MEASURES: High-density genome-wide single-nucleotide polymorphism arrays, along with microsatellite analysis, and genetic linkage studies were performed. Whole-exome sequencing was used for 2 affected relatives. For most patients, the initial symptoms included falls, dysarthria, or clumsiness followed by a complete cerebellar syndrome. For all 9 affected relatives, we observed altered vertical eye movements, as initial ocular signs for 3 of them and for the 2 asymptomatic family members, all having inherited the risk haplotype. Neuroimaging showed isolated cerebellar atrophy. RESULTS: Initial genome-wide linkage analysis revealed suggestive linkage to chromosome 1p32. Multipoint analysis and haplotype reconstruction further traced this SCA locus to a 0.66-cM interval flanked by D1S200 and D1S2742 (z(max) = 6.539; P < .0001). The causative mutation was unidentified by exome sequencing. CONCLUSIONS AND RELEVANCE: We report a new subtype of SCA presenting in patients as slow progressing ataxia with altered vertical eye movements linked to a 11-megabase interval on 1p32. The Human Genome Nomenclature Committee has assigned this subtype of ataxia the designation SCA37. |
Materia(s):
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-Gens Mapatge |
Derechos:
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© American Medical Association. All Rights Reserved.
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Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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American Institute of Physics (AIP)
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