title: New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Primary care institutional center in Spain.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Neurology Unit, Department of Internal Medicine, Hospital St Joan de Deu, Martorell, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Serrano-Munuera
authors.forename: Marc
authors.initials: M
authors.lastname: Corral-Juan
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Hector
authors.initials: H
authors.lastname: San Nicolás
authors.forename: Carles
authors.initials: C
authors.lastname: Roig
authors.forename: Jordi
authors.initials: J
authors.lastname: Corral
authors.forename: Berta
authors.initials: B
authors.lastname: Campos
authors.forename: Laura
authors.initials: L
authors.lastname: de Jorge
authors.forename: Carlos
authors.initials: C
authors.lastname: Morcillo-Suárez
authors.forename: Arcadi
authors.initials: A
authors.lastname: Navarro
authors.forename: Sylvie
authors.initials: S
authors.lastname: Forlani
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Jaime
authors.initials: J
authors.lastname: Kulisevsky
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Ivelisse
authors.initials: I
authors.lastname: Sánchez
authors.forename: Victor
authors.initials: V
authors.lastname: Volpini
authors.forename: Antoni
authors.initials: A
authors.lastname: Matilla-Dueñas
mesh_terms: D000328:Adult; D002874:Chromosome Mapping / Q000379:methods; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005133:Eye Movements / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015835:Ocular Motility Disorders / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*