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New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32.

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.

journal_name

JAMA Neurol

journal_title

JAMA neurology

authors

Serrano-Munuera C,Corral-Juan M,Stevanin G,San Nicolás H,Roig C,Corral J,Campos B,de Jorge L,Morcillo-Suárez C,Navarro A,Forlani S,Durr A,Kulisevsky J,Brice A,Sánchez I,Volpini V,Matilla-Dueñas A

doi

10.1001/jamaneurol.2013.2311

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

764-71

issue

eissn

2168-6149

issn

2168-6157

pii

1682611

journal_volume

pub_type

杂志文章,多中心研究

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New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32.