New Subtype of Spinocerebellar Ataxia With Altered Vertical Eye Movements Mapping to Chromosome 1p32

作者：Serrano Munuera Carmen; Corral Juan Marc; Stevanin Giovanni; San Nicolas Hector; Roig Carles; Corral Jordi; Campos Berta; de Jorge Laura; Morcillo Suarez Carlos; Navarro Arcadi; Forlani Sylvie; Durr Alexandra; Kulisevsky Jaime; Brice Alexis; Sanchez Ivelisse; Volpini Victor; Matilla Duenas Antoni^*

来源：JAMA Neurology, 2013, 70(6): 764-771.

DOI：10.1001/jamaneurol.2013.2311

Importance: To provide clinical and genetic diagnoses for patients%26apos; conditions, it is important to identify and characterize the different subtypes of spinocerebellar ataxia (SCA). %26lt;br%26gt;Objective: To clinically and genetically characterize a Spanish kindred with pure SCA presenting with altered vertical eye movements. %26lt;br%26gt;Design: Family study of ambulatory patients. Electro-oculographic and genetics studies were performed in 2 referral university centers. %26lt;br%26gt;Setting: Primary care institutional center in Spain. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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 %26lt; .0001). The causative mutation was unidentified by exome sequencing. %26lt;br%26gt;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.

• 出版日期2013-6