dc.contributor.author |
Serrano Munuera, Carmen |
dc.contributor.author |
Corral Juan, Marc |
dc.contributor.author |
Stevanin, Giovanni |
dc.contributor.author |
San Nicolás, Hector |
dc.contributor.author |
Roig, Carles |
dc.contributor.author |
Corral, Jordi |
dc.contributor.author |
Campos, Berta |
dc.contributor.author |
Jorge, Laura de |
dc.contributor.author |
Morcillo Suárez, Carlos, 1969- |
dc.contributor.author |
Navarro i Cuartiellas, Arcadi, 1969- |
dc.contributor.author |
Forlani, Sylvie |
dc.contributor.author |
Durr, Alexandra |
dc.contributor.author |
Kulisevsky, Jaime J. |
dc.contributor.author |
Brice, Alexis |
dc.contributor.author |
Sánchez, Ivelisse |
dc.contributor.author |
Volpini, Victor |
dc.contributor.author |
Matilla Dueñas, Antoni |
dc.date |
2013 |
dc.identifier.citation |
Serrano-Munuera C, Corral-Juan M, Stevanin G, San Nicolás H, Roig C, Corral J et al. New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32. JAMA neurology. 2013. 70(6): 764-771. DOI 10.1001/jamaneurol.2013.2311 |
dc.identifier.citation |
2168-6149 |
dc.identifier.citation |
http://dx.doi.org/10.1001/jamaneurol.2013.2311 |
dc.identifier.uri |
http://hdl.handle.net/10230/25315 |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
American Institute of Physics (AIP) |
dc.relation |
JAMA neurology. 2013. 70(6): 764-771 |
dc.rights |
© American Medical Association. All Rights Reserved. |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Gens Mapatge |
dc.title |
New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32 |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/publishedVersion |
dc.description.abstract |
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. |